PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 31654721-1 2020 The fusion oncogene, promyelocytic leukemia (PML)-retinoic acid receptor-alpha (RARalpha), is crucial for acute promyelocytic leukemia (APL) pathogenesis. Tretinoin 50-63 PML nuclear body scaffold Homo sapiens 45-48 31447065-2 2019 While most cases of APL harboring the PML/RARA fusion respond to all-trans retinoic acid (ATRA), some variant RARA rearrangements are ATRA insensitive. Tretinoin 68-88 PML nuclear body scaffold Homo sapiens 38-41 31905996-4 2019 Since we demonstrated how high doses of ascorbate (ASC) preferentially kill leukemic blast cells from APL patients, we aimed to define the underlying mechanism and found that promyelocytic leukemia/retinoic acid receptor alpha (PML/RARa) inhibits NRF2 function, impedes its transfer to the nucleus and enhances its degradation in the cytoplasm. Tretinoin 198-211 PML nuclear body scaffold Homo sapiens 228-236 31592194-0 2019 KDM3B suppresses APL progression by restricting chromatin accessibility and facilitating the ATRA-mediated degradation of PML/RARalpha. Tretinoin 93-97 PML nuclear body scaffold Homo sapiens 122-125 31592194-10 2019 Moreover, knocking down KDM3B inhibited the ATRA-induced degradation of the PML/RARalpha oncoprotein. Tretinoin 44-48 PML nuclear body scaffold Homo sapiens 76-79 31592194-11 2019 Conclusion: Our study suggested that KDM3B was able to inhibit APL progression by maintaining chromatin in a compact state and facilitating the ATRA-mediated degradation of PML/RARalpha. Tretinoin 144-148 PML nuclear body scaffold Homo sapiens 173-176 31292998-6 2019 In patients relapsing after ATRA/ATO, the PML gene was a preferential mutation target. Tretinoin 28-32 PML nuclear body scaffold Homo sapiens 42-45 31447065-2 2019 While most cases of APL harboring the PML/RARA fusion respond to all-trans retinoic acid (ATRA), some variant RARA rearrangements are ATRA insensitive. Tretinoin 90-94 PML nuclear body scaffold Homo sapiens 38-41 28291070-8 2019 CONCLUSION: Acute promyelocytic leukemia treated with ATRA may result in upregulation of vascular endothelial growth factor in retinal tissues. Tretinoin 54-58 PML nuclear body scaffold Homo sapiens 18-40 30876657-8 2019 Results of PML IF influenced decision to start ATRA in 25 (36%) APL patients and led to its termination in six non-APL patients. Tretinoin 47-51 PML nuclear body scaffold Homo sapiens 11-14 31135261-1 2019 Transcriptional activation by PML-RARalpha, an acute promyelocytic leukemia-related oncofusion protein, requires pharmacological concentrations of all-trans retinoic acid (ATRA). Tretinoin 157-170 PML nuclear body scaffold Homo sapiens 30-33 31135261-1 2019 Transcriptional activation by PML-RARalpha, an acute promyelocytic leukemia-related oncofusion protein, requires pharmacological concentrations of all-trans retinoic acid (ATRA). Tretinoin 172-176 PML nuclear body scaffold Homo sapiens 30-33 31135261-4 2019 Luciferase reporter assays showed that PML-RARalpha induced significant transcription at pharmacological doses (1 muM) of ATRA; however, this was submaximal and equivalent to the level of transcription driven by intact RARalpha at physiological doses (1 nM) of ATRA. Tretinoin 122-126 PML nuclear body scaffold Homo sapiens 39-42 31135261-4 2019 Luciferase reporter assays showed that PML-RARalpha induced significant transcription at pharmacological doses (1 muM) of ATRA; however, this was submaximal and equivalent to the level of transcription driven by intact RARalpha at physiological doses (1 nM) of ATRA. Tretinoin 261-265 PML nuclear body scaffold Homo sapiens 39-42 30824184-1 2019 Genetic mutations on PML-RARalpha in acute promyelocytic leukemia (APL) are reported to associate with arsenic trioxide (ATO) or all-trans retinoic acid (ATRA) resistance. Tretinoin 139-152 PML nuclear body scaffold Homo sapiens 21-24 30824184-1 2019 Genetic mutations on PML-RARalpha in acute promyelocytic leukemia (APL) are reported to associate with arsenic trioxide (ATO) or all-trans retinoic acid (ATRA) resistance. Tretinoin 154-158 PML nuclear body scaffold Homo sapiens 21-24 30824184-2 2019 Here we performed a retrospective analysis of APL patients and identified that the patient with S214L mutation on the PML moiety of PML-RARalpha showed resistance to both ATO and ATRA. Tretinoin 179-183 PML nuclear body scaffold Homo sapiens 118-121 30824184-2 2019 Here we performed a retrospective analysis of APL patients and identified that the patient with S214L mutation on the PML moiety of PML-RARalpha showed resistance to both ATO and ATRA. Tretinoin 179-183 PML nuclear body scaffold Homo sapiens 132-135 31135261-7 2019 These results suggest that PML-RARalpha initiates ATRA-induced transcription through its interaction with MED1. Tretinoin 50-54 PML nuclear body scaffold Homo sapiens 27-30 30992691-9 2019 Compared with PML-RARA, GTF2I-RARA has a higher affinity to HDAC3 under ATRA treatment. Tretinoin 72-76 PML nuclear body scaffold Homo sapiens 14-17 30289902-0 2018 Identification of the novel deletion-type PML-RARA mutation associated with the retinoic acid resistance in acute promyelocytic leukemia. Tretinoin 80-93 PML nuclear body scaffold Homo sapiens 42-45 30536958-6 2019 We show that in vitro treatment of PML/RARA expressing cells with all-trans retinoic acid (ATRA) up-regulates HSP90 expression and stabilizes AKT. Tretinoin 76-89 PML nuclear body scaffold Homo sapiens 35-38 30536958-6 2019 We show that in vitro treatment of PML/RARA expressing cells with all-trans retinoic acid (ATRA) up-regulates HSP90 expression and stabilizes AKT. Tretinoin 91-95 PML nuclear body scaffold Homo sapiens 35-38 30572725-1 2019 INTRODUCTION: The outcome of acute promyelocytic leukemia (APL) has drastically improved following the identification of the PML-RARA oncogene as a key player in the pathogenesis of APL, and the subsequent introduction of all-trans retinoic acid (ATRA) as a therapeutic agent. Tretinoin 247-251 PML nuclear body scaffold Homo sapiens 125-128 30662778-4 2018 We describe the efficacy and feasibility of the consecutive use of all-trans retinoic acid and arsenic trioxide-containing regimen for the treatment of promyelocytic leukemia and high-dose methotrexate plus cytarabine to treat lymphoproliferative involvement of the central nervous system. Tretinoin 77-90 PML nuclear body scaffold Homo sapiens 152-174 30289902-8 2018 In deletion PML-RARA-transduced cells, the CD11b expression levels and NBT reducing ability were significantly decreased compared with control cells and the formation of PML nuclear bodies was rarely observed after RA treatment. Tretinoin 16-18 PML nuclear body scaffold Homo sapiens 12-15 30289902-8 2018 In deletion PML-RARA-transduced cells, the CD11b expression levels and NBT reducing ability were significantly decreased compared with control cells and the formation of PML nuclear bodies was rarely observed after RA treatment. Tretinoin 16-18 PML nuclear body scaffold Homo sapiens 170-173 30289902-6 2018 To clarify the biological significance of the identified PML-RARA mutations, we analyzed the ATRA-induced differentiation and PML nuclear body formation in mutant PML-RARA-transduced HL-60 cells. Tretinoin 93-97 PML nuclear body scaffold Homo sapiens 57-60 30289902-7 2018 At molecular relapse, the p.K227_T233del deletion and the p.R217S point-mutation in the RARA region of PML-RARA were identified, and their frequencies increased after re-induction therapy with another type of retinoiec acid (RA), tamibarotene. Tretinoin 88-90 PML nuclear body scaffold Homo sapiens 103-106 30026570-3 2018 Moreover, PML/RARA is specifically targeted by All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), two agents that synergistically act to induce degradation of the oncoprotein. Tretinoin 47-70 PML nuclear body scaffold Homo sapiens 10-13 30026570-3 2018 Moreover, PML/RARA is specifically targeted by All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), two agents that synergistically act to induce degradation of the oncoprotein. Tretinoin 72-76 PML nuclear body scaffold Homo sapiens 10-13 29795382-1 2018 Retinoic acid (RA) and arsenic target the t(15;17)(q24;q21) PML/RARA driver of acute promyelocytic leukemia (APL), their combination now curing over 95% patients. Tretinoin 0-13 PML nuclear body scaffold Homo sapiens 60-63 29795382-1 2018 Retinoic acid (RA) and arsenic target the t(15;17)(q24;q21) PML/RARA driver of acute promyelocytic leukemia (APL), their combination now curing over 95% patients. Tretinoin 15-17 PML nuclear body scaffold Homo sapiens 60-63 29795382-6 2018 Accordingly, clonogenic activity of PML/RARA-immortalized progenitors ex vivo is only transiently affected by RA, but selectively abrogated by arsenic. Tretinoin 40-42 PML nuclear body scaffold Homo sapiens 36-39 29596829-5 2018 Recent studies suggest that pharmacological concentrations of the APL therapeutic drugs, all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), affect post-mitotic nuclear import of the APL-associated oncoprotein PML/RARA. Tretinoin 89-112 PML nuclear body scaffold Homo sapiens 217-220 29596829-5 2018 Recent studies suggest that pharmacological concentrations of the APL therapeutic drugs, all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), affect post-mitotic nuclear import of the APL-associated oncoprotein PML/RARA. Tretinoin 114-118 PML nuclear body scaffold Homo sapiens 217-220 28521962-6 2018 All-trans retinoic acid and arsenic trioxide treatment has been implemented for promyelocytic leukemia to target the PML-RARalpha fusion protein. Tretinoin 10-23 PML nuclear body scaffold Homo sapiens 117-120 30114705-9 2018 RESULTS: MAT improved the sensitivity of NB4-LR1cells to ATRA treatment, which was consistent with the expression of PML-RARalpha fusion protein. Tretinoin 57-61 PML nuclear body scaffold Homo sapiens 117-120 28712407-1 2017 Objective To study the expression patterns of promyelocytic leukemia (PML) protein at different stages of acute promyelocytic leukemia (APL) and investigate the effects that the arsenical, all-trans retinoic acid (ATRA) and chemotherapeutic drugs on PML protein expression patterns. Tretinoin 214-218 PML nuclear body scaffold Homo sapiens 70-73 29224413-9 2018 Interestingly, the combination of GSK-J4 and all-trans retinoic acid (ATRA) significantly increased PML-RARalpha-positive cell apoptosis compared with ATRA treatment alone. Tretinoin 45-68 PML nuclear body scaffold Homo sapiens 100-103 29224413-9 2018 Interestingly, the combination of GSK-J4 and all-trans retinoic acid (ATRA) significantly increased PML-RARalpha-positive cell apoptosis compared with ATRA treatment alone. Tretinoin 70-74 PML nuclear body scaffold Homo sapiens 100-103 29973452-2 2018 The advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as molecular targeted therapies directed against PML-RARalpha has been a major breakthrough in APL treatment. Tretinoin 14-37 PML nuclear body scaffold Homo sapiens 121-124 29973452-2 2018 The advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as molecular targeted therapies directed against PML-RARalpha has been a major breakthrough in APL treatment. Tretinoin 39-43 PML nuclear body scaffold Homo sapiens 121-124 29387217-1 2018 Acute promyelocytic leukemia (APL), characterized by the presence of the promyelocytic leukemia (PML)-retinoic acid alpha receptor (RARalpha) fusion protein, responds to treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Tretinoin 102-115 PML nuclear body scaffold Homo sapiens 97-100 29387217-1 2018 Acute promyelocytic leukemia (APL), characterized by the presence of the promyelocytic leukemia (PML)-retinoic acid alpha receptor (RARalpha) fusion protein, responds to treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Tretinoin 210-214 PML nuclear body scaffold Homo sapiens 97-100 28766684-5 2017 EGCG in synergy with ATRA promote degradation of PML/RARalpha and restores PML expression, and increase the level of nuclear PTEN. Tretinoin 21-25 PML nuclear body scaffold Homo sapiens 49-52 28766684-5 2017 EGCG in synergy with ATRA promote degradation of PML/RARalpha and restores PML expression, and increase the level of nuclear PTEN. Tretinoin 21-25 PML nuclear body scaffold Homo sapiens 75-78 28712407-5 2017 Compared with control group without medication, the PML protein expression of APL cells in initial onset cases had larger fluorescent signals in the ATRA group, As2O3 group and As4S4 group, whereas there were no significant changes in the arabinoside cytosine group and the homoharringtonine group. Tretinoin 149-153 PML nuclear body scaffold Homo sapiens 52-55 28486108-6 2017 Genetically inhibiting TRIB3 expression or combination of a peptide disturbing TRIB3/PML-RARalpha interaction with ATRA/As2O3 eradicates APL by accelerating PML-RARalpha degradation. Tretinoin 115-119 PML nuclear body scaffold Homo sapiens 85-88 28492552-1 2017 All-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) administration leads to granulocytic maturation and/or apoptosis of acute promyelocytic leukemia (APL) cells mainly by targeting promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha). Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 243-246 28492552-1 2017 All-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) administration leads to granulocytic maturation and/or apoptosis of acute promyelocytic leukemia (APL) cells mainly by targeting promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha). Tretinoin 25-29 PML nuclear body scaffold Homo sapiens 243-246 28492552-2 2017 Yet, ~10-15% of APL patients are not cured by ATRA- and ATO-based therapies, and a potential failure of ATRA and ATO in completely reversing PML/RARalpha-driven oncogenic alterations has not been comprehensively examined. Tretinoin 104-108 PML nuclear body scaffold Homo sapiens 141-144 28486108-6 2017 Genetically inhibiting TRIB3 expression or combination of a peptide disturbing TRIB3/PML-RARalpha interaction with ATRA/As2O3 eradicates APL by accelerating PML-RARalpha degradation. Tretinoin 115-119 PML nuclear body scaffold Homo sapiens 157-160 28063140-3 2017 We used real-time quantitative PCR to determine whether PML/RARalpha affects the expression of S100A9 in NB4 and PR9 cells upon ATRA treatment. Tretinoin 128-132 PML nuclear body scaffold Homo sapiens 56-59 28063140-9 2017 Collectively, our data indicated that PML/RARalpha and PU.1 were necessary for the ATRA-induced expression of S100A9 in APL cells. Tretinoin 83-87 PML nuclear body scaffold Homo sapiens 38-41 28959333-1 2016 BACKGROUND: Promyelocytic leukemia protein (PML) is a tumor suppressor protein that is involved in myeloid cell differentiation in response to retinoic acid (RA). Tretinoin 143-156 PML nuclear body scaffold Homo sapiens 12-42 27605212-0 2017 Activation of G0S2 is coordinated by recruitment of PML/RARalpha and C/EBPepsilon to its promoter during ATRA-induced APL differentiation. Tretinoin 105-109 PML nuclear body scaffold Homo sapiens 52-55 27605212-1 2017 All-trans retinoic acid (ATRA) binds the promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha) fusion protein and is an effective oncogene-targeted therapy for acute promyelocytic leukemia (APL). Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 94-97 27605212-1 2017 All-trans retinoic acid (ATRA) binds the promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha) fusion protein and is an effective oncogene-targeted therapy for acute promyelocytic leukemia (APL). Tretinoin 25-29 PML nuclear body scaffold Homo sapiens 94-97 27605212-2 2017 However, the molecular basis of PML/RARalpha-mediated transcriptional control during ATRA-induced differentiation is unclear. Tretinoin 85-89 PML nuclear body scaffold Homo sapiens 32-35 27605212-4 2017 Here, we performed a series of chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR) experiments, demonstrating that there is an additional mode of action of PML/RARalpha, wherein PML/RARalpha does not bind DNA in the absence of ATRA but binds DNA and activates adjacent genes in the presence of ATRA. Tretinoin 236-240 PML nuclear body scaffold Homo sapiens 165-168 27605212-4 2017 Here, we performed a series of chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR) experiments, demonstrating that there is an additional mode of action of PML/RARalpha, wherein PML/RARalpha does not bind DNA in the absence of ATRA but binds DNA and activates adjacent genes in the presence of ATRA. Tretinoin 236-240 PML nuclear body scaffold Homo sapiens 187-190 27605212-4 2017 Here, we performed a series of chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR) experiments, demonstrating that there is an additional mode of action of PML/RARalpha, wherein PML/RARalpha does not bind DNA in the absence of ATRA but binds DNA and activates adjacent genes in the presence of ATRA. Tretinoin 303-307 PML nuclear body scaffold Homo sapiens 165-168 27605212-4 2017 Here, we performed a series of chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR) experiments, demonstrating that there is an additional mode of action of PML/RARalpha, wherein PML/RARalpha does not bind DNA in the absence of ATRA but binds DNA and activates adjacent genes in the presence of ATRA. Tretinoin 303-307 PML nuclear body scaffold Homo sapiens 187-190 28129653-2 2017 All-trans retinoic acid (ATRA) and arsenic trioxide cure most patients by directly targeting PML-RARalpha. Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 93-96 28129653-2 2017 All-trans retinoic acid (ATRA) and arsenic trioxide cure most patients by directly targeting PML-RARalpha. Tretinoin 25-29 PML nuclear body scaffold Homo sapiens 93-96 27740626-5 2017 We further revealed that the downregulation of HOTAIRM1 could inhibit all-trans retinoic acid (ATRA) -induced degradation of PML-RARA in APL cells and repress the process of differentiation from promyelocytic to granulocytic cells. Tretinoin 80-93 PML nuclear body scaffold Homo sapiens 125-128 27740626-5 2017 We further revealed that the downregulation of HOTAIRM1 could inhibit all-trans retinoic acid (ATRA) -induced degradation of PML-RARA in APL cells and repress the process of differentiation from promyelocytic to granulocytic cells. Tretinoin 95-99 PML nuclear body scaffold Homo sapiens 125-128 27133819-0 2016 PML-RARalpha kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy. Tretinoin 117-121 PML nuclear body scaffold Homo sapiens 0-3 27133819-0 2016 PML-RARalpha kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy. Tretinoin 133-137 PML nuclear body scaffold Homo sapiens 0-3 30695510-2 2017 All-trans retinoic acid (ATRA) is a representa- tive molecular-targeted drug and is directed against PML-RARA. Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 101-104 30695510-2 2017 All-trans retinoic acid (ATRA) is a representa- tive molecular-targeted drug and is directed against PML-RARA. Tretinoin 25-29 PML nuclear body scaffold Homo sapiens 101-104 27888400-5 2016 Furthermore, all-trans retinoic acid treatment induced CDKN2C expression by releasing the PML/RARalpha binding on chromatin in NB4 cells. Tretinoin 23-36 PML nuclear body scaffold Homo sapiens 90-93 27732960-3 2016 Based on the known interaction of redox-active selenium compounds with thiolate ligands of zinc, we herein have investigated the abrogatory effects of selenite alone or in combination with all-trans retinoic acid on PML/RARalpha and the possible effects on differentiation in these cells. Tretinoin 199-212 PML nuclear body scaffold Homo sapiens 216-219 27626069-3 2016 Thirteen months after the start of ATRA maintenance, the patient suffered clinically overt meningeal relapse along with minute molecular traces of PML/RARA (promyelocytic leukemia/retinoic acid receptor alpha) in the bone marrow. Tretinoin 35-39 PML nuclear body scaffold Homo sapiens 147-155 28959333-1 2016 BACKGROUND: Promyelocytic leukemia protein (PML) is a tumor suppressor protein that is involved in myeloid cell differentiation in response to retinoic acid (RA). Tretinoin 143-156 PML nuclear body scaffold Homo sapiens 44-47 28959333-1 2016 BACKGROUND: Promyelocytic leukemia protein (PML) is a tumor suppressor protein that is involved in myeloid cell differentiation in response to retinoic acid (RA). Tretinoin 158-160 PML nuclear body scaffold Homo sapiens 12-42 28959333-1 2016 BACKGROUND: Promyelocytic leukemia protein (PML) is a tumor suppressor protein that is involved in myeloid cell differentiation in response to retinoic acid (RA). Tretinoin 158-160 PML nuclear body scaffold Homo sapiens 44-47 27468685-2 2016 All-trans-retinoic acid (RA) treatment induces PML-RARalpha degradation, restores PML-NB functions, and causes terminal cell differentiation of APL blasts. Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 47-50 27486764-6 2016 We also show that let-7 microRNA family members promote differentiation of All-Trans-Retinoic Acid (ATRA)-induced NB4 cells and their activities are affected by expression levels of both c-Myc and PML/RARalpha through altering miRNA targets. Tretinoin 85-98 PML nuclear body scaffold Homo sapiens 197-200 27486764-6 2016 We also show that let-7 microRNA family members promote differentiation of All-Trans-Retinoic Acid (ATRA)-induced NB4 cells and their activities are affected by expression levels of both c-Myc and PML/RARalpha through altering miRNA targets. Tretinoin 100-104 PML nuclear body scaffold Homo sapiens 197-200 27468685-2 2016 All-trans-retinoic acid (RA) treatment induces PML-RARalpha degradation, restores PML-NB functions, and causes terminal cell differentiation of APL blasts. Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 82-85 27468685-2 2016 All-trans-retinoic acid (RA) treatment induces PML-RARalpha degradation, restores PML-NB functions, and causes terminal cell differentiation of APL blasts. Tretinoin 25-27 PML nuclear body scaffold Homo sapiens 47-50 27468685-2 2016 All-trans-retinoic acid (RA) treatment induces PML-RARalpha degradation, restores PML-NB functions, and causes terminal cell differentiation of APL blasts. Tretinoin 25-27 PML nuclear body scaffold Homo sapiens 82-85 26997274-2 2016 From a retinoic acid (RA)-sensitive acute promyelocytic leukemia (APL) cell line, we derived an RA-resistant clone characterized by a block in transcription initiation, despite maintaining wild-type PML/RARA expression. Tretinoin 96-98 PML nuclear body scaffold Homo sapiens 199-202 25759405-1 2015 The majority of patients with acute promyelocytic leukaemia (APL) carry the hallmark t(15;17)(q22;q21) translocation, involving the promyelocytic leukaemia/retinoic acid receptor-alpha (PML/RARalpha) fusion gene, and by sensitivity of blast cells to all-trans retinoic acid (ATRA) and/or arsenic trioxide therapy. Tretinoin 275-279 PML nuclear body scaffold Homo sapiens 186-189 26728337-2 2016 PML and RARA mutations have been shown to directly respond to arsenic trioxide (ATO) and all-trans retinoic (ATRA). Tretinoin 109-113 PML nuclear body scaffold Homo sapiens 0-3 25795919-2 2015 Oncoprotein targeting can be a successful strategy to treat AML, as proved in acute promyelocytic leukemia by treatment with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO), which degrade the promyelocytic leukemia (PML)-retinoic acid receptor fusion protein. Tretinoin 125-148 PML nuclear body scaffold Homo sapiens 227-230 25795919-2 2015 Oncoprotein targeting can be a successful strategy to treat AML, as proved in acute promyelocytic leukemia by treatment with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO), which degrade the promyelocytic leukemia (PML)-retinoic acid receptor fusion protein. Tretinoin 150-154 PML nuclear body scaffold Homo sapiens 227-230 25800051-5 2015 Combined RA/arsenic treatment significantly reduced bone marrow blasts in 3 patients and restored the subnuclear localization of both NPM1 and PML. Tretinoin 9-11 PML nuclear body scaffold Homo sapiens 143-146 26374632-2 2016 We explored these questions in the context of acute promyelocytic leukemia cells (NB4) expressing oncogenic fusion protein, PML-RARa and exquisitely sensitive to its clinically used antagonist, the all-trans retinoic acid (ATRA). Tretinoin 208-221 PML nuclear body scaffold Homo sapiens 124-127 26374632-2 2016 We explored these questions in the context of acute promyelocytic leukemia cells (NB4) expressing oncogenic fusion protein, PML-RARa and exquisitely sensitive to its clinically used antagonist, the all-trans retinoic acid (ATRA). Tretinoin 223-227 PML nuclear body scaffold Homo sapiens 124-127 26058416-4 2015 It has been found that all-trans-retinoic acid (ATRA) or arsenic trioxide (ATO) alone exerts therapeutic effect on APL patients with the PML-RARalpha fusion gene, and the combination of both drugs can act synergistically to further enhance the cure rate of the patients. Tretinoin 23-46 PML nuclear body scaffold Homo sapiens 137-140 26058416-4 2015 It has been found that all-trans-retinoic acid (ATRA) or arsenic trioxide (ATO) alone exerts therapeutic effect on APL patients with the PML-RARalpha fusion gene, and the combination of both drugs can act synergistically to further enhance the cure rate of the patients. Tretinoin 48-52 PML nuclear body scaffold Homo sapiens 137-140 26775483-6 2015 RESULTS: MAT combined ATRA could significantly elevate positive rates of NBT and CD11 b in NB4-R1 cells, and significantly down-regulate the expression of PML/RARapha-fusion protein/gene (P < 0.05, P < 0.01). Tretinoin 22-26 PML nuclear body scaffold Homo sapiens 155-158 26775483-13 2015 CONCLUSION: MAT combined ATRA could significantly induce the differentiation of NB4-R1 cells, and inhibit the expression of PML/RARalpha fusion gene/protein, which might be associated with up-regulating PLSCR1 expression. Tretinoin 25-29 PML nuclear body scaffold Homo sapiens 124-127 25849135-4 2015 ATRA-induced Pin1 ablation degrades the protein encoded by the fusion oncogene PML-RARA and treats APL in APL cell and animal models as well as in human patients. Tretinoin 0-4 PML nuclear body scaffold Homo sapiens 79-82 25973309-7 2015 HMGB1 regulated the interactions between ubiquitin-binding adaptor protein p62/SQSTM and PML-RARalpha so as to affect the degradation of PML-RARalpha during ATRA-induced autophagy. Tretinoin 157-161 PML nuclear body scaffold Homo sapiens 89-92 25514379-3 2015 All-trans-retinoic acid (ATRA) induces the proteasomal degradation of PML-RARalpha and granulocytic differentiation. Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 70-73 25514379-3 2015 All-trans-retinoic acid (ATRA) induces the proteasomal degradation of PML-RARalpha and granulocytic differentiation. Tretinoin 25-29 PML nuclear body scaffold Homo sapiens 70-73 25973309-2 2015 As a fusion protein of promyelocytic leukemia (PML) and retinoic acid receptor-alpha (RARalpha), PML-RARalpha oncoprotein is degraded through the differentiation of all-trans retinoic acid (ATRA)-induced cells. Tretinoin 56-69 PML nuclear body scaffold Homo sapiens 97-100 25973309-2 2015 As a fusion protein of promyelocytic leukemia (PML) and retinoic acid receptor-alpha (RARalpha), PML-RARalpha oncoprotein is degraded through the differentiation of all-trans retinoic acid (ATRA)-induced cells. Tretinoin 190-194 PML nuclear body scaffold Homo sapiens 47-50 25973309-2 2015 As a fusion protein of promyelocytic leukemia (PML) and retinoic acid receptor-alpha (RARalpha), PML-RARalpha oncoprotein is degraded through the differentiation of all-trans retinoic acid (ATRA)-induced cells. Tretinoin 190-194 PML nuclear body scaffold Homo sapiens 97-100 25692052-11 2015 Similar to APL with chromosomal translocations other than classical t(15;17) which result in the typical PML-RARA fusion, our patient responded promptly to an ATRA-containing regimen and remains in complete remission. Tretinoin 159-163 PML nuclear body scaffold Homo sapiens 105-108 26862315-2 2015 The discovery of all-trans retinoic acid (ATRA), which acts directly on promyelocytic locus-retinoic acid receptor alpha (PML-RARalpha) gene product, brought a revolution to the therapy of this disorder. Tretinoin 17-40 PML nuclear body scaffold Homo sapiens 122-125 26862315-2 2015 The discovery of all-trans retinoic acid (ATRA), which acts directly on promyelocytic locus-retinoic acid receptor alpha (PML-RARalpha) gene product, brought a revolution to the therapy of this disorder. Tretinoin 42-46 PML nuclear body scaffold Homo sapiens 122-125 26637766-2 2015 Acute promyelocytic leukemia (APL) is characterized commonly by a fusion between the PML gene and the RARA gene, genes targetable by arsenic (ATO) and retinoic acid (ATRA), respectively. Tretinoin 151-164 PML nuclear body scaffold Homo sapiens 85-88 26637766-2 2015 Acute promyelocytic leukemia (APL) is characterized commonly by a fusion between the PML gene and the RARA gene, genes targetable by arsenic (ATO) and retinoic acid (ATRA), respectively. Tretinoin 166-170 PML nuclear body scaffold Homo sapiens 85-88 25973309-7 2015 HMGB1 regulated the interactions between ubiquitin-binding adaptor protein p62/SQSTM and PML-RARalpha so as to affect the degradation of PML-RARalpha during ATRA-induced autophagy. Tretinoin 157-161 PML nuclear body scaffold Homo sapiens 137-140 24592821-2 2014 However, in the majority of patients given all-trans retinoic acid (ATRA)/anthracycline-based induction therapy, PML-RARalpha transcript remains even when haematologic complete remission is achieved. Tretinoin 68-72 PML nuclear body scaffold Homo sapiens 113-116 25258343-4 2014 Whereas RA elicits transcriptional activation of PML/RARA targets, how arsenic triggers differentiation remains unclear. Tretinoin 8-10 PML nuclear body scaffold Homo sapiens 49-52 25126724-4 2014 MIR125B1 overexpression enhanced PML-RARA expression and inhibited the ATRA-induced degradation of the PML-RARA oncoprotein. Tretinoin 71-75 PML nuclear body scaffold Homo sapiens 103-106 24592821-2 2014 However, in the majority of patients given all-trans retinoic acid (ATRA)/anthracycline-based induction therapy, PML-RARalpha transcript remains even when haematologic complete remission is achieved. Tretinoin 43-66 PML nuclear body scaffold Homo sapiens 113-116 23770850-3 2014 We report here the regulatory mechanism of the repression of PU.1-dependent activation of PSMBs by PML/RARalpha in the pathogenesis of acute promyelocytic leukemia (APL) and the unidentified function of all-trans retinoic acid (ATRA) as an immunomodulator in the treatment of APL. Tretinoin 228-232 PML nuclear body scaffold Homo sapiens 99-102 23770850-9 2014 Collectively, our data demonstrate that PML/RARalpha suppresses PU.1-dependent activation of the immunosubunits, which may facilitate the escape of APL cells from immune surveillance in leukemia development, and ATRA treatment is able to reactivate their expression, which would promote more efficient T-cell-mediated recognition in the treatment. Tretinoin 212-216 PML nuclear body scaffold Homo sapiens 40-43 22964640-4 2013 In particular, PML/RARalpha-positive blasts from APL patients display lower levels of miRNA let-7c, a member of the let-7 family, than normal promyelocytes and its expression increases after ATRA treatment. Tretinoin 191-195 PML nuclear body scaffold Homo sapiens 15-18 24566867-3 2014 In acute promyelocytic leukemia (APL), repression by the PML-RARalpha oncofusion protein is mediated by an HDAC-containing complex that can be dissociated by pharmacologic doses of all trans retinoic acid (ATRA) inducing differentiation and cell death at the expense of side effects and recurrence. Tretinoin 191-204 PML nuclear body scaffold Homo sapiens 57-60 24566867-3 2014 In acute promyelocytic leukemia (APL), repression by the PML-RARalpha oncofusion protein is mediated by an HDAC-containing complex that can be dissociated by pharmacologic doses of all trans retinoic acid (ATRA) inducing differentiation and cell death at the expense of side effects and recurrence. Tretinoin 206-210 PML nuclear body scaffold Homo sapiens 57-60 24566867-4 2014 We hypothesized that the context-specific close physical proximity of a retinoid and HDACi-binding protein in the repressive PML-RARalpha-HDAC complex may permit selective targeting by a hybrid molecule of ATRA with a 2-aminoanilide tail of the HDAC inhibitor MS-275, yielding MC2392. Tretinoin 206-210 PML nuclear body scaffold Homo sapiens 125-128 23998577-0 2013 Expression of PML-RARalpha is up-regulated during ATRA and arsenics combined induction without influence on long-term prognosis of acute promyelocytic leukemia. Tretinoin 50-54 PML nuclear body scaffold Homo sapiens 14-17 23998577-9 2013 It is concluded that up-regulation of PML-RARa expression is a common event during induction therapy with ATRA plus arsenics. Tretinoin 106-110 PML nuclear body scaffold Homo sapiens 38-41 24907012-6 2014 More recently, arsenic trioxide (ATO) has been shown to contribute degradation of the PML-RARalpha oncoprotein through bonding the PML moiety and has shown excellent synergism with ATRA in clinical trials. Tretinoin 181-185 PML nuclear body scaffold Homo sapiens 86-89 24907012-6 2014 More recently, arsenic trioxide (ATO) has been shown to contribute degradation of the PML-RARalpha oncoprotein through bonding the PML moiety and has shown excellent synergism with ATRA in clinical trials. Tretinoin 181-185 PML nuclear body scaffold Homo sapiens 131-134 24596215-1 2014 PML-RARA degradation and PML nuclear body reformation underlie APL clearance by retinoic acid (RA). Tretinoin 80-93 PML nuclear body scaffold Homo sapiens 0-3 24596215-1 2014 PML-RARA degradation and PML nuclear body reformation underlie APL clearance by retinoic acid (RA). Tretinoin 80-93 PML nuclear body scaffold Homo sapiens 25-28 24596215-1 2014 PML-RARA degradation and PML nuclear body reformation underlie APL clearance by retinoic acid (RA). Tretinoin 4-6 PML nuclear body scaffold Homo sapiens 0-3 24344243-3 2013 The empirical discoveries that PML-RARa-associated APL is sensitive to both all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO), and the subsequent understanding of the mechanisms of action of these drugs, have led to efforts to understand the contribution of molecular events to APL cell differentiation, leukemia-initiating cell (LIC) clearance, and disease eradication in vitro and in vivo. Tretinoin 76-99 PML nuclear body scaffold Homo sapiens 31-34 24344243-3 2013 The empirical discoveries that PML-RARa-associated APL is sensitive to both all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO), and the subsequent understanding of the mechanisms of action of these drugs, have led to efforts to understand the contribution of molecular events to APL cell differentiation, leukemia-initiating cell (LIC) clearance, and disease eradication in vitro and in vivo. Tretinoin 101-105 PML nuclear body scaffold Homo sapiens 31-34 23670176-3 2013 Genetic mutations resulting in amino acid substitution in the retinoic acid receptor alpha (RARalpha) ligand binding domain (LBD) and the PML-B2 domain of PML-RARalpha, respectively, have been reported as molecular mechanisms underlying resistance to ATRA and As2O3. Tretinoin 251-255 PML nuclear body scaffold Homo sapiens 138-141 23627671-0 2013 The short isoform of the long-type PML-RARA fusion gene in acute promyelocytic leukaemia lacks sensitivity to all-trans-retinoic acid. Tretinoin 110-133 PML nuclear body scaffold Homo sapiens 35-38 23670176-3 2013 Genetic mutations resulting in amino acid substitution in the retinoic acid receptor alpha (RARalpha) ligand binding domain (LBD) and the PML-B2 domain of PML-RARalpha, respectively, have been reported as molecular mechanisms underlying resistance to ATRA and As2O3. Tretinoin 251-255 PML nuclear body scaffold Homo sapiens 155-158 23098119-3 2012 The molecular hallmark of the disease is the presence of a balanced reciprocal translocation resulting in the PML/RAR-alpha gene fusion, which represents the target of the all-trans retinoic acid (ATRA) therapy. Tretinoin 182-195 PML nuclear body scaffold Homo sapiens 110-123 22845560-8 2012 This work provides novel experimental evidence of the beneficial role of the DNMT inhibitor RG108 in combinations with RA and HDACIs in the effective differentiation of human PML based on epigenetics. Tretinoin 119-121 PML nuclear body scaffold Homo sapiens 175-178 23159843-2 2013 Rapid detection of the PML-RARA fusion gene provides the molecular basis for a highly effective therapy with all-trans retinoic acid. Tretinoin 119-132 PML nuclear body scaffold Homo sapiens 23-26 23155234-1 2012 A deficient retinoic acid signaling has been suggested to be an important cause of the clinical inefficacy of all-trans retinoic acid (ATRA) therapy in non-promyelocytic (non-PML) forms of acute myeloid leukemia (AML). Tretinoin 12-25 PML nuclear body scaffold Homo sapiens 175-178 23098119-3 2012 The molecular hallmark of the disease is the presence of a balanced reciprocal translocation resulting in the PML/RAR-alpha gene fusion, which represents the target of the all-trans retinoic acid (ATRA) therapy. Tretinoin 197-201 PML nuclear body scaffold Homo sapiens 110-123 23049403-4 2012 The immunofluorescence staining technique using the anti-PML antibody may be used to provide a rapid diagnosis and to immediately start therapy using all-trans retinoic acid. Tretinoin 160-173 PML nuclear body scaffold Homo sapiens 57-60 22969967-10 2012 Together, IFN-gamma augments the proliferation inhibition effect of ATRA on NB4 and NB4-R1 cells through enhancing the expression of PML protein. Tretinoin 68-72 PML nuclear body scaffold Homo sapiens 133-136 22406747-1 2012 Acute promyelocytic leukemia (APL), a cytogenetically distinct subtype of acute myeloid leukemia (AML), characterized by the t(15;17)-associated PML-RARA fusion, has been successfully treated with therapy utilizing all-trans-retinoic acid (ATRA) to differentiate leukemic blasts. Tretinoin 215-238 PML nuclear body scaffold Homo sapiens 145-148 22406747-1 2012 Acute promyelocytic leukemia (APL), a cytogenetically distinct subtype of acute myeloid leukemia (AML), characterized by the t(15;17)-associated PML-RARA fusion, has been successfully treated with therapy utilizing all-trans-retinoic acid (ATRA) to differentiate leukemic blasts. Tretinoin 240-244 PML nuclear body scaffold Homo sapiens 145-148 23300507-0 2012 Anti-PML-RARalpha shRNA sensitises promyelocytic leukaemia cells to all-trans retinoic acid. Tretinoin 78-91 PML nuclear body scaffold Homo sapiens 5-8 23300507-4 2012 When combined with ATRA administration, this down regulation of the fusion gene strongly inhibited proliferation in the NB4 PML cell line. Tretinoin 19-23 PML nuclear body scaffold Homo sapiens 124-127 21422471-6 2011 All-trans retinoic acid, which targets PML-RARalpha for degradation through its RARalpha moiety, synergizes with arsenic in eliminating leukemia-initiating cells. Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 39-42 21859732-1 2011 BACKGROUND: Combined treatment with all-trans-retinoic acid and chemotherapy is extremely efficient in patients with acute promyelocytic leukemia with t(15;17)/PML-RARA, but up to 15% of patients relapse. Tretinoin 36-59 PML nuclear body scaffold Homo sapiens 160-163 22040992-2 2011 As a subtype of acute myeloid leukemia, acute promyelocytic leukemia (APL) represents the target of therapy due to the good response of the oncogenic protein PML-RARalpha to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Tretinoin 184-197 PML nuclear body scaffold Homo sapiens 158-161 22040992-2 2011 As a subtype of acute myeloid leukemia, acute promyelocytic leukemia (APL) represents the target of therapy due to the good response of the oncogenic protein PML-RARalpha to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Tretinoin 199-203 PML nuclear body scaffold Homo sapiens 158-161 22586354-4 2011 In acute promyelocytic leukemia, the cooperative degradation of PML/RARA by arsenic and retinoic acid cures most patients. Tretinoin 88-101 PML nuclear body scaffold Homo sapiens 64-67 21790894-6 2011 The introduction of drugs such as all-trans retinoic acid (ATRA) that promote progenitor differentiation by directly inhibiting the PML-RARalpha fusion protein has changed the treatment paradigm for APL and markedly improved patient survival. Tretinoin 34-57 PML nuclear body scaffold Homo sapiens 132-135 21790894-6 2011 The introduction of drugs such as all-trans retinoic acid (ATRA) that promote progenitor differentiation by directly inhibiting the PML-RARalpha fusion protein has changed the treatment paradigm for APL and markedly improved patient survival. Tretinoin 59-63 PML nuclear body scaffold Homo sapiens 132-135 21360626-0 2011 Promyelocytic leukemia protein in retinoic acid-induced chromatin remodeling of Oct4 gene promoter. Tretinoin 34-47 PML nuclear body scaffold Homo sapiens 0-30 21187718-2 2011 A hallmark of all-trans retinoic acid (ATRA) responses in APL is PML-RARalpha degradation which promotes cell differentiation. Tretinoin 24-37 PML nuclear body scaffold Homo sapiens 65-68 21187718-2 2011 A hallmark of all-trans retinoic acid (ATRA) responses in APL is PML-RARalpha degradation which promotes cell differentiation. Tretinoin 39-43 PML nuclear body scaffold Homo sapiens 65-68 21187718-7 2011 Furthermore, knockdown of p62/SQSTM1 inhibited ATRA-induced PML-RARalpha degradation and myeloid cell differentiation. Tretinoin 47-51 PML nuclear body scaffold Homo sapiens 60-63 21360626-3 2011 Retinoic acid (RA) rapidly downregulates Pml, resulting in the replacement of BRGC with Brm-containing remodeling complex, disassociation of SF1 and Sp1, retaining of TR2, recruitment of receptor-interaction protein 140, G9a and HP1gamma, and sequential insertion of two nucleosomes on CR1 that progressively displays repressive heterochromatin marks. Tretinoin 0-13 PML nuclear body scaffold Homo sapiens 41-44 20935222-2 2010 APL cell treatment with all-trans-retinoic acid (RA) degrades the chimeric, dominant-negative-acting transcription factor promyelocytic leukemia gene (PML)/RARalpha, which is generated in APL by chromosomal translocation. Tretinoin 24-47 PML nuclear body scaffold Homo sapiens 122-149 20935222-2 2010 APL cell treatment with all-trans-retinoic acid (RA) degrades the chimeric, dominant-negative-acting transcription factor promyelocytic leukemia gene (PML)/RARalpha, which is generated in APL by chromosomal translocation. Tretinoin 24-47 PML nuclear body scaffold Homo sapiens 151-154 20935222-2 2010 APL cell treatment with all-trans-retinoic acid (RA) degrades the chimeric, dominant-negative-acting transcription factor promyelocytic leukemia gene (PML)/RARalpha, which is generated in APL by chromosomal translocation. Tretinoin 49-51 PML nuclear body scaffold Homo sapiens 122-149 20935222-2 2010 APL cell treatment with all-trans-retinoic acid (RA) degrades the chimeric, dominant-negative-acting transcription factor promyelocytic leukemia gene (PML)/RARalpha, which is generated in APL by chromosomal translocation. Tretinoin 49-51 PML nuclear body scaffold Homo sapiens 151-154 20528759-4 2010 All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which are the major molecularly targeted therapies in APL, affect the PML/RARA fusion protein and cause differentiation and apoptosis of APL cells. Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 129-132 20528759-4 2010 All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which are the major molecularly targeted therapies in APL, affect the PML/RARA fusion protein and cause differentiation and apoptosis of APL cells. Tretinoin 25-29 PML nuclear body scaffold Homo sapiens 129-132 20574048-1 2010 Treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid and/or arsenic trioxide represents a paradigm in targeted cancer therapy because these drugs cause clinical remission by affecting the stability of the fusion oncoprotein promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARA). Tretinoin 63-76 PML nuclear body scaffold Homo sapiens 272-275 20574048-4 2010 We found that both all-trans retinoic acid and arsenic trioxide induce autophagy via the mammalian target of rapamycin pathway in APL cells and that autophagic degradation contributes significantly both to the basal turnover as well as the therapy-induced proteolysis of PML/RARA. Tretinoin 29-42 PML nuclear body scaffold Homo sapiens 271-274 20615082-0 2010 Arsenic trioxide cooperates with all trans retinoic acid to enhance mitogen-activated protein kinase activation and differentiation in PML-RARalpha negative human myeloblastic leukemia cells. Tretinoin 43-56 PML nuclear body scaffold Homo sapiens 135-138 20615082-1 2010 Arsenic trioxide (ATO) synergistically promotes all trans retinoic acid (ATRA)-induced differentiation of PML-RARalpha negative HL-60 myeloblastic leukemia cells. Tretinoin 58-71 PML nuclear body scaffold Homo sapiens 106-109 20615082-1 2010 Arsenic trioxide (ATO) synergistically promotes all trans retinoic acid (ATRA)-induced differentiation of PML-RARalpha negative HL-60 myeloblastic leukemia cells. Tretinoin 73-77 PML nuclear body scaffold Homo sapiens 106-109 20615082-8 2010 In summary, our results indicate that ATO in conjunction with ATRA is of potential chemotherapeutic use in PML-RARalpha negative leukemias. Tretinoin 62-66 PML nuclear body scaffold Homo sapiens 107-110 20084480-1 2010 Retinoic acid (RA), similar to specific growth factors, can induce differentiation of proliferating promyelocytic precursors into terminally differentiated granulocytes, although little is known about effects of its 13-cis isomer on promyelocytic leukemia (PML). Tretinoin 0-13 PML nuclear body scaffold Homo sapiens 257-260 20084480-1 2010 Retinoic acid (RA), similar to specific growth factors, can induce differentiation of proliferating promyelocytic precursors into terminally differentiated granulocytes, although little is known about effects of its 13-cis isomer on promyelocytic leukemia (PML). Tretinoin 15-17 PML nuclear body scaffold Homo sapiens 257-260 20455087-3 2010 Both retinoic acid (RA) and arsenic trioxide directly target PML/RARA-mediated transcriptional repression and protein stability, inducing rapid differentiation of the promyelocytes and clinical remission in most APL patients. Tretinoin 5-18 PML nuclear body scaffold Homo sapiens 61-64 20455087-3 2010 Both retinoic acid (RA) and arsenic trioxide directly target PML/RARA-mediated transcriptional repression and protein stability, inducing rapid differentiation of the promyelocytes and clinical remission in most APL patients. Tretinoin 20-22 PML nuclear body scaffold Homo sapiens 61-64 19749800-8 2009 In addition, we observed, in response to ATRA, the release of PML/RARalpha paralleled by their transcriptional activation, together with their host genes, EVL and C21orf34alpha. Tretinoin 41-45 PML nuclear body scaffold Homo sapiens 62-65 20224268-3 2010 The data presented in this study demonstrated that ider(17q), which resulted in an extra RARA-PML fusion gene, was more frequent in males than females (male/female ratio of 2.12/1), was associated with a rather low initial white blood cell count and did not confer an adverse prognosis in APL patients treated with all-trans-retinoic acid and chemotherapy. Tretinoin 319-338 PML nuclear body scaffold Homo sapiens 94-97 19273155-4 2009 The treatment of APL patients with all-transretinoic acid (ATRA) and arsenic trioxide which target the PML-RARA oncoprotein results in clinical remission, associated with blast cell differentiation and reformation of the PML NBs, thus linking NB integrity with disease status. Tretinoin 35-57 PML nuclear body scaffold Homo sapiens 103-106 19155306-0 2009 Inhibition of the peptidyl-prolyl-isomerase Pin1 enhances the responses of acute myeloid leukemia cells to retinoic acid via stabilization of RARalpha and PML-RARalpha. Tretinoin 107-120 PML nuclear body scaffold Homo sapiens 155-158 19702568-2 2009 All-trans retinoic acid (ATRA) and arsenic trioxide, which are the major molecularly targeted therapies in APL, affect or degrade the PML/RARA fusion protein and cause differentiation and apoptosis of APL cells. Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 134-137 19702568-2 2009 All-trans retinoic acid (ATRA) and arsenic trioxide, which are the major molecularly targeted therapies in APL, affect or degrade the PML/RARA fusion protein and cause differentiation and apoptosis of APL cells. Tretinoin 25-29 PML nuclear body scaffold Homo sapiens 134-137 19451220-6 2009 Upon treatment with ATRA, ectopic recruitment of PRC2 by either PML/RARA or PLZF/RARA is lost, whereas PRC1 recruited by PLZF/RARA remains, resulting in persistent RA-insensitive gene repression. Tretinoin 20-24 PML nuclear body scaffold Homo sapiens 64-67 19273155-4 2009 The treatment of APL patients with all-transretinoic acid (ATRA) and arsenic trioxide which target the PML-RARA oncoprotein results in clinical remission, associated with blast cell differentiation and reformation of the PML NBs, thus linking NB integrity with disease status. Tretinoin 35-57 PML nuclear body scaffold Homo sapiens 221-224 19273155-4 2009 The treatment of APL patients with all-transretinoic acid (ATRA) and arsenic trioxide which target the PML-RARA oncoprotein results in clinical remission, associated with blast cell differentiation and reformation of the PML NBs, thus linking NB integrity with disease status. Tretinoin 59-63 PML nuclear body scaffold Homo sapiens 103-106 19273155-4 2009 The treatment of APL patients with all-transretinoic acid (ATRA) and arsenic trioxide which target the PML-RARA oncoprotein results in clinical remission, associated with blast cell differentiation and reformation of the PML NBs, thus linking NB integrity with disease status. Tretinoin 59-63 PML nuclear body scaffold Homo sapiens 221-224 18716620-6 2008 Remarkably, treatment with drugs that trigger PML-RARalpha degradation, such as all-trans retinoic acid or arsenic trioxide, restore nuclear PTEN. Tretinoin 80-103 PML nuclear body scaffold Homo sapiens 46-49 19204783-7 2009 Recently, we found that all-trans retinoic acid (atRA) triggers the activation of extracellular-signal-regulated kinase 2 (ERK2), which phosphorylates TR2 and stimulates its partitioning to promyelocytic leukemia (PML) nuclear bodies, thereby converting the activator function of TR2 into repression (Gupta et al. Tretinoin 24-47 PML nuclear body scaffold Homo sapiens 214-217 19041605-2 2008 Most patients are treated with all-trans retinoic acid (ATRA), which targets the RAR-alpha moiety of the PML/RAR-alpha fusion transcript, and anthracycline-based chemotherapy. Tretinoin 41-54 PML nuclear body scaffold Homo sapiens 105-118 19041605-2 2008 Most patients are treated with all-trans retinoic acid (ATRA), which targets the RAR-alpha moiety of the PML/RAR-alpha fusion transcript, and anthracycline-based chemotherapy. Tretinoin 56-60 PML nuclear body scaffold Homo sapiens 105-118 18534676-1 2008 The nuclear arrangement of promyelocytic leukaemia nuclear bodies (PML NBs) was studied in vitro after the cell treatment by clinically used agents such as all-trans retinoic acid (RA) in human leukaemia and cytostatics or gamma radiation in multiple myeloma cells. Tretinoin 181-183 PML nuclear body scaffold Homo sapiens 67-70 18534676-3 2008 A reduced number of PML bodies, which led to relocation of PML NBs closer to the nuclear interior, mostly accompanied RA- and PMA-induced differentiation. Tretinoin 118-120 PML nuclear body scaffold Homo sapiens 20-23 18534676-3 2008 A reduced number of PML bodies, which led to relocation of PML NBs closer to the nuclear interior, mostly accompanied RA- and PMA-induced differentiation. Tretinoin 118-120 PML nuclear body scaffold Homo sapiens 59-62 18413804-11 2008 These findings confirmed that RA triggers PML/RARalpha degradation through different domains and distinct mechanisms. Tretinoin 30-32 PML nuclear body scaffold Homo sapiens 42-45 18682553-0 2008 Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression. Tretinoin 0-13 PML nuclear body scaffold Homo sapiens 53-56 18636162-1 2008 All-trans-retinoic acid (RA) treatment of acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, PML/RARalpha, is a successful example of differentiation therapy. Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 116-119 18636162-1 2008 All-trans-retinoic acid (RA) treatment of acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, PML/RARalpha, is a successful example of differentiation therapy. Tretinoin 25-27 PML nuclear body scaffold Homo sapiens 116-119 18445086-2 2008 PML/RARalpha is directly targeted by all-trans-retinoic acid (ATRA), which degrades the oncoprotein and induces complete remission of malignancies. Tretinoin 37-60 PML nuclear body scaffold Homo sapiens 0-3 18445086-2 2008 PML/RARalpha is directly targeted by all-trans-retinoic acid (ATRA), which degrades the oncoprotein and induces complete remission of malignancies. Tretinoin 62-66 PML nuclear body scaffold Homo sapiens 0-3 18413804-2 2008 RA treatment can confer PML/RARalpha degradation, overcoming dominant-negative effects of this oncogenic protein. Tretinoin 0-2 PML nuclear body scaffold Homo sapiens 24-27 18413804-4 2008 RA treatment is known to repress PML/RARalpha and augment ubiquitin-activating enzyme-E1-like (UBE1L) protein expression in NB4-S1 APL cells. Tretinoin 0-2 PML nuclear body scaffold Homo sapiens 33-36 18025157-2 2008 At physiological concentrations of retinoic acid, PML-RARalpha silences RARalpha target genes, blocking differentiation of the cells. Tretinoin 35-48 PML nuclear body scaffold Homo sapiens 50-53 19204783-7 2009 Recently, we found that all-trans retinoic acid (atRA) triggers the activation of extracellular-signal-regulated kinase 2 (ERK2), which phosphorylates TR2 and stimulates its partitioning to promyelocytic leukemia (PML) nuclear bodies, thereby converting the activator function of TR2 into repression (Gupta et al. Tretinoin 49-53 PML nuclear body scaffold Homo sapiens 214-217 18039708-4 2008 We show a functional RA response element in the DIF2 promoter, which is constitutively bound by PML/RARalpha in APL cells. Tretinoin 21-23 PML nuclear body scaffold Homo sapiens 96-99 16740359-0 2007 Retinoic acid attenuates promyelocytic leukemia protein-induced cell death in breast cancer cells by activation of the ubiquitin-proteasome pathway. Tretinoin 0-13 PML nuclear body scaffold Homo sapiens 25-55 17991421-6 2008 In addition, we revealed that co-repressor SMRT co-localized with PML-RARalpha, resulting in the immobilization of SMRT while ATRA treatment eliminated their association and reversed the immobile effect of SMRT. Tretinoin 126-130 PML nuclear body scaffold Homo sapiens 66-69 17986232-4 2008 Using two different human neuroblastoma cell lines, SH-SY5Y and LA-N-5, we show here that PML protein leads to the formation of nuclear bodies (PML-NB) after only 1 h of retinoic acid treatment and that this formation is mediated by the extracellular signal-regulated kinase (ERK) pathway. Tretinoin 170-183 PML nuclear body scaffold Homo sapiens 90-93 17986232-4 2008 Using two different human neuroblastoma cell lines, SH-SY5Y and LA-N-5, we show here that PML protein leads to the formation of nuclear bodies (PML-NB) after only 1 h of retinoic acid treatment and that this formation is mediated by the extracellular signal-regulated kinase (ERK) pathway. Tretinoin 170-183 PML nuclear body scaffold Homo sapiens 144-147 17929112-0 2007 PML-RARalpha inhibitors (ATRA, tamibaroten, arsenic troxide) for acute promyelocytic leukemia. Tretinoin 25-29 PML nuclear body scaffold Homo sapiens 0-3 17317642-16 2007 Strikingly, a clearance of PML-RARalpha transcript in an earlier and more thorough manner, and a higher quality remission and survival in newly diagnosed APL are achieved when ATRA is combined with ATO, as compared to either monotherapy, making APL a curable disease. Tretinoin 176-180 PML nuclear body scaffold Homo sapiens 27-30 17475621-8 2007 Furthermore, treatment of NB4 cells with all-trans-retinoic acid, which promotes PML-RARalpha degradation, resulted in increased activation of GILZ. Tretinoin 41-64 PML nuclear body scaffold Homo sapiens 81-84 16740359-5 2007 We concluded that PML and all-trans-retinoic acid cause cell death by different pathways: PML activates ERK1/2, p38 MAPK, and p21; arrests the cell cycle; and later causes cell death; and all-trans-retinoic acid activates proteasome function, caspase cleavage, and apoptosis. Tretinoin 26-49 PML nuclear body scaffold Homo sapiens 90-93 16740359-5 2007 We concluded that PML and all-trans-retinoic acid cause cell death by different pathways: PML activates ERK1/2, p38 MAPK, and p21; arrests the cell cycle; and later causes cell death; and all-trans-retinoic acid activates proteasome function, caspase cleavage, and apoptosis. Tretinoin 188-211 PML nuclear body scaffold Homo sapiens 18-21 16740359-6 2007 The combined use of all-trans-retinoic acid and PML gene therapy may not be the best treatment for patients with cancer, because the ubiquitinylation of PML and its subsequent proteasome-dependent degradation by retinoic acids occur before overexpressed PML exhibits tumor-suppressive activity. Tretinoin 20-43 PML nuclear body scaffold Homo sapiens 153-156 16740359-6 2007 The combined use of all-trans-retinoic acid and PML gene therapy may not be the best treatment for patients with cancer, because the ubiquitinylation of PML and its subsequent proteasome-dependent degradation by retinoic acids occur before overexpressed PML exhibits tumor-suppressive activity. Tretinoin 20-43 PML nuclear body scaffold Homo sapiens 153-156 16740359-6 2007 The combined use of all-trans-retinoic acid and PML gene therapy may not be the best treatment for patients with cancer, because the ubiquitinylation of PML and its subsequent proteasome-dependent degradation by retinoic acids occur before overexpressed PML exhibits tumor-suppressive activity. Tretinoin 212-226 PML nuclear body scaffold Homo sapiens 48-51 16740359-6 2007 The combined use of all-trans-retinoic acid and PML gene therapy may not be the best treatment for patients with cancer, because the ubiquitinylation of PML and its subsequent proteasome-dependent degradation by retinoic acids occur before overexpressed PML exhibits tumor-suppressive activity. Tretinoin 212-226 PML nuclear body scaffold Homo sapiens 153-156 16740359-6 2007 The combined use of all-trans-retinoic acid and PML gene therapy may not be the best treatment for patients with cancer, because the ubiquitinylation of PML and its subsequent proteasome-dependent degradation by retinoic acids occur before overexpressed PML exhibits tumor-suppressive activity. Tretinoin 212-226 PML nuclear body scaffold Homo sapiens 153-156 17001604-5 2006 Transient cotransfection assay revealed that PML-RARalpha is a potent activator of OP18 promoter and this transcriptional activation is retinoic acid sensitive. Tretinoin 136-149 PML nuclear body scaffold Homo sapiens 45-48 17202112-2 2007 Patients with APL respond to differentiation therapy with all-trans-retinoic acid, which induces PML/RAR alpha degradation. Tretinoin 58-81 PML nuclear body scaffold Homo sapiens 97-110 17468032-2 2007 The ability of retinoic acid (RA) and arsenic trioxide to directly target the oncogenic promyelocytic leukemia-retinoic receptor A (PML-RARA) fusion protein also made this disease the first model for oncogene-targeted therapies. Tretinoin 15-28 PML nuclear body scaffold Homo sapiens 132-135 17468032-2 2007 The ability of retinoic acid (RA) and arsenic trioxide to directly target the oncogenic promyelocytic leukemia-retinoic receptor A (PML-RARA) fusion protein also made this disease the first model for oncogene-targeted therapies. Tretinoin 30-32 PML nuclear body scaffold Homo sapiens 132-135 16832676-7 2006 However, the histone acetylase inhibitor SAHA combined with ATRA significantly reactivated RARbeta2 mRNA both in NB4 and MR2 cells with degradation of PML-RARalpha, which was associated with maturation. Tretinoin 60-64 PML nuclear body scaffold Homo sapiens 151-154 16935935-0 2006 Retinoic acid induces leukemia cell G1 arrest and transition into differentiation by inhibiting cyclin-dependent kinase-activating kinase binding and phosphorylation of PML/RARalpha. Tretinoin 0-13 PML nuclear body scaffold Homo sapiens 169-172 16935935-6 2006 In response to ATRA, PML/RARalpha is dissociated from CAK, leading to MAT1 degradation, G1 arrest, and decreased CAK phosphorylation of PML/RARalpha. Tretinoin 15-19 PML nuclear body scaffold Homo sapiens 21-24 16935935-6 2006 In response to ATRA, PML/RARalpha is dissociated from CAK, leading to MAT1 degradation, G1 arrest, and decreased CAK phosphorylation of PML/RARalpha. Tretinoin 15-19 PML nuclear body scaffold Homo sapiens 136-139 16935935-8 2006 Both MAT1 degradation and PML/RARalpha hypophosphorylation occur in ATRA-induced G1-arresting cells undergoing differentiation but not in the synchronized G1 cells that do not differentiate. Tretinoin 68-72 PML nuclear body scaffold Homo sapiens 26-29 16434964-4 2006 PML-RARalpha has been shown to promote transcriptional repression of genes involved in myeloid terminal differentiation and to disrupt the architecture of PML bodies, a phenotype reversed by treatment with all trans retinoic acid (ATRA). Tretinoin 216-229 PML nuclear body scaffold Homo sapiens 0-3 16835227-7 2006 PML/RARalpha in APL suppresses Chk2 by dominantly inhibiting the auto-phosphorylation step, but inactivation of PML/RARalpha with alltrans retinoic acid (ATRA) restores Chk2 autophosphorylation and activity. Tretinoin 139-152 PML nuclear body scaffold Homo sapiens 0-3 16835227-7 2006 PML/RARalpha in APL suppresses Chk2 by dominantly inhibiting the auto-phosphorylation step, but inactivation of PML/RARalpha with alltrans retinoic acid (ATRA) restores Chk2 autophosphorylation and activity. Tretinoin 139-152 PML nuclear body scaffold Homo sapiens 112-115 16835227-7 2006 PML/RARalpha in APL suppresses Chk2 by dominantly inhibiting the auto-phosphorylation step, but inactivation of PML/RARalpha with alltrans retinoic acid (ATRA) restores Chk2 autophosphorylation and activity. Tretinoin 154-158 PML nuclear body scaffold Homo sapiens 0-3 16835227-7 2006 PML/RARalpha in APL suppresses Chk2 by dominantly inhibiting the auto-phosphorylation step, but inactivation of PML/RARalpha with alltrans retinoic acid (ATRA) restores Chk2 autophosphorylation and activity. Tretinoin 154-158 PML nuclear body scaffold Homo sapiens 112-115 16636064-6 2006 Following RA treatment, we also observed increased nuclear EBBP levels in aggregates with the promyelocytic leukemia protein at promyelocytic leukemia nuclear bodies. Tretinoin 10-12 PML nuclear body scaffold Homo sapiens 94-124 16434964-4 2006 PML-RARalpha has been shown to promote transcriptional repression of genes involved in myeloid terminal differentiation and to disrupt the architecture of PML bodies, a phenotype reversed by treatment with all trans retinoic acid (ATRA). Tretinoin 216-229 PML nuclear body scaffold Homo sapiens 155-158 16434964-4 2006 PML-RARalpha has been shown to promote transcriptional repression of genes involved in myeloid terminal differentiation and to disrupt the architecture of PML bodies, a phenotype reversed by treatment with all trans retinoic acid (ATRA). Tretinoin 231-235 PML nuclear body scaffold Homo sapiens 0-3 16434964-4 2006 PML-RARalpha has been shown to promote transcriptional repression of genes involved in myeloid terminal differentiation and to disrupt the architecture of PML bodies, a phenotype reversed by treatment with all trans retinoic acid (ATRA). Tretinoin 231-235 PML nuclear body scaffold Homo sapiens 155-158 16434964-8 2006 The activity of the PML-RARalphaL is completely sensitive to ATRA. Tretinoin 61-65 PML nuclear body scaffold Homo sapiens 20-23 16540467-7 2006 Remarkably, Mut PML stabilizes PML-RARalpha and inhibits differentiation induced by pharmacological doses of RA. Tretinoin 35-37 PML nuclear body scaffold Homo sapiens 16-19 16540467-7 2006 Remarkably, Mut PML stabilizes PML-RARalpha and inhibits differentiation induced by pharmacological doses of RA. Tretinoin 35-37 PML nuclear body scaffold Homo sapiens 31-34 16437139-1 2006 Relapse of acute promyelocytic leukemia (APL) following all-trans retinoic acid (ATRA) therapy has been associated with the acquisition of mutations in the high-affinity ATRA binding site in PML-RARalpha, but little information is available about the selection dynamics of the mutation-harboring subclones. Tretinoin 66-79 PML nuclear body scaffold Homo sapiens 191-194 16437139-1 2006 Relapse of acute promyelocytic leukemia (APL) following all-trans retinoic acid (ATRA) therapy has been associated with the acquisition of mutations in the high-affinity ATRA binding site in PML-RARalpha, but little information is available about the selection dynamics of the mutation-harboring subclones. Tretinoin 81-85 PML nuclear body scaffold Homo sapiens 191-194 16437139-1 2006 Relapse of acute promyelocytic leukemia (APL) following all-trans retinoic acid (ATRA) therapy has been associated with the acquisition of mutations in the high-affinity ATRA binding site in PML-RARalpha, but little information is available about the selection dynamics of the mutation-harboring subclones. Tretinoin 170-174 PML nuclear body scaffold Homo sapiens 191-194 16437139-2 2006 In this study, 6/18 patients treated with sequential ATRA and chemotherapy on protocol INT0129 relapsed with complete replacement of the nonmutant pretreatment APL cell population by a PML-RARalpha mutant subclone. Tretinoin 53-57 PML nuclear body scaffold Homo sapiens 185-188 15748426-4 2005 The ability of ATRA to modify the recruitment of nuclear receptor co-repressor with PML-RAR alpha but not PLZF-RAR alpha caused by the variant chromosome translocation elucidated the therapeutic mechanism of ATRA from the molecular level and provides new insight into transcription-modulating therapy. Tretinoin 15-19 PML nuclear body scaffold Homo sapiens 84-87 16501610-3 2006 In the NB4 cell line, which was derived from an APL patient and expresses PML:RARalpha, we observed a retinoic acid-dependent change in the modification of specific proteins by SUMO-1. Tretinoin 102-115 PML nuclear body scaffold Homo sapiens 74-77 16331271-11 2006 Similarly to what was observed in human APL patients, we found that NPM/RAR alpha and PML/RAR alpha, but not PLZF/RAR alpha leukemia, was responsive to all-trans retinoic acid (ATRA) or As2O3 treatments. Tretinoin 162-175 PML nuclear body scaffold Homo sapiens 86-99 16331271-11 2006 Similarly to what was observed in human APL patients, we found that NPM/RAR alpha and PML/RAR alpha, but not PLZF/RAR alpha leukemia, was responsive to all-trans retinoic acid (ATRA) or As2O3 treatments. Tretinoin 177-181 PML nuclear body scaffold Homo sapiens 86-99 16405439-4 2006 We report a unique case of a PML/RARA positive APL patient exhibiting extensive monocytic differentiation after ATRA therapy as documented by morphology, flow cytometry, and FISH studies. Tretinoin 112-116 PML nuclear body scaffold Homo sapiens 29-32 17124055-4 2006 The unique PML/RARalpha aberration serves as a molecular marker for rapid diagnosis and prediction of response to ATRA-and ATO-containing therapies. Tretinoin 114-118 PML nuclear body scaffold Homo sapiens 11-14 16375665-5 2005 This PML-RAR alpha fusion protein is responsible for the proliferative and de-differentiated phenotype of the leukemic cells and is the target of all-trans retinoic acid (ATRA). Tretinoin 156-169 PML nuclear body scaffold Homo sapiens 5-8 16375665-5 2005 This PML-RAR alpha fusion protein is responsible for the proliferative and de-differentiated phenotype of the leukemic cells and is the target of all-trans retinoic acid (ATRA). Tretinoin 171-175 PML nuclear body scaffold Homo sapiens 5-8 16112651-6 2005 We found that retinoic acid that dissociates PML-RARalpha from the DNA, and which is used to treat acute promyelocytic leukemia patients, restores heparanase expression to normal levels in an acute promyelocytic leukemia cell line. Tretinoin 14-27 PML nuclear body scaffold Homo sapiens 45-48 15746941-3 2005 The results show that CDDO-Im selectively downregulates expression of the PML/retinoic receptor alpha fusion protein by a caspase-dependent mechanism and sensitizes APL cells to the differentiating effects of all-trans retinoic acid (ATRA). Tretinoin 219-232 PML nuclear body scaffold Homo sapiens 74-77 15746941-3 2005 The results show that CDDO-Im selectively downregulates expression of the PML/retinoic receptor alpha fusion protein by a caspase-dependent mechanism and sensitizes APL cells to the differentiating effects of all-trans retinoic acid (ATRA). Tretinoin 234-238 PML nuclear body scaffold Homo sapiens 74-77 16187701-1 2005 The results of the treatment of 14 patients with promyelocytic leukemia (PML) treated with all trans-retinoic acid (ATRA), combined chemotherapy (CT) and prophylactic prednisone are reported; the median age was 30 years (range 7 - 49). Tretinoin 95-114 PML nuclear body scaffold Homo sapiens 49-71 16187701-1 2005 The results of the treatment of 14 patients with promyelocytic leukemia (PML) treated with all trans-retinoic acid (ATRA), combined chemotherapy (CT) and prophylactic prednisone are reported; the median age was 30 years (range 7 - 49). Tretinoin 95-114 PML nuclear body scaffold Homo sapiens 73-76 16187701-1 2005 The results of the treatment of 14 patients with promyelocytic leukemia (PML) treated with all trans-retinoic acid (ATRA), combined chemotherapy (CT) and prophylactic prednisone are reported; the median age was 30 years (range 7 - 49). Tretinoin 116-120 PML nuclear body scaffold Homo sapiens 49-71 16187701-1 2005 The results of the treatment of 14 patients with promyelocytic leukemia (PML) treated with all trans-retinoic acid (ATRA), combined chemotherapy (CT) and prophylactic prednisone are reported; the median age was 30 years (range 7 - 49). Tretinoin 116-120 PML nuclear body scaffold Homo sapiens 73-76 15358589-4 2004 The t(15;17)(q22;q21) gene rearrangement and PML/RARalpha fusion product in acute promyelocytic leukemia played the key role to leukemogenesis and to sensitivity to differentiation-inducing therapy of all-trans retinoic acid. Tretinoin 211-224 PML nuclear body scaffold Homo sapiens 45-48 15529177-10 2005 RA enhanced the expression of adenovirus-cytomegalovirus-promoted PML at both transcription and protein levels within 12 hours after treatment; however, the PML protein was significantly degraded in the presence of RA at days 3-5 postinfection. Tretinoin 0-2 PML nuclear body scaffold Homo sapiens 66-69 15529177-10 2005 RA enhanced the expression of adenovirus-cytomegalovirus-promoted PML at both transcription and protein levels within 12 hours after treatment; however, the PML protein was significantly degraded in the presence of RA at days 3-5 postinfection. Tretinoin 215-217 PML nuclear body scaffold Homo sapiens 157-160 15529177-11 2005 PML degradation was also observed in SK-BR3 breast cancer cells treated with RA. Tretinoin 77-79 PML nuclear body scaffold Homo sapiens 0-3 15529177-12 2005 Taken together, our findings strongly support the hypothesis that PML acts as a strong independent cell death inducer and that RA conversely abolishes the therapeutic effects of the PML proteins through proteasomal degradation of the protein. Tretinoin 127-129 PML nuclear body scaffold Homo sapiens 182-185 15319284-2 2004 Acute promyelocytic leukemia (APL) is characterized by a translocation, t(15;17), that produces a PML/RARalpha fusion oncoprotein, whose abnormal transcriptional function is successfully targeted by pharmacologic levels of all-trans-retinoic acid (ATRA). Tretinoin 226-246 PML nuclear body scaffold Homo sapiens 98-101 15319284-2 2004 Acute promyelocytic leukemia (APL) is characterized by a translocation, t(15;17), that produces a PML/RARalpha fusion oncoprotein, whose abnormal transcriptional function is successfully targeted by pharmacologic levels of all-trans-retinoic acid (ATRA). Tretinoin 248-252 PML nuclear body scaffold Homo sapiens 98-101 15319284-7 2004 This effect may not be limited to abnormal nuclear receptors, because overexpression of SMRTbeta increased ATRA-induced binding and transcriptional activation of wild-type receptors PML/RARalpha and RARalpha. Tretinoin 107-111 PML nuclear body scaffold Homo sapiens 182-185 15512805-4 2004 It is now well established that all-trans-retinoic acid when administered at pharmacological doses can reverse the dominant-negative effects that the PML-RARalpha oncoprotein exhibits on the functions of the wild type PML and RARalpha proteins. Tretinoin 32-55 PML nuclear body scaffold Homo sapiens 150-153 15512805-4 2004 It is now well established that all-trans-retinoic acid when administered at pharmacological doses can reverse the dominant-negative effects that the PML-RARalpha oncoprotein exhibits on the functions of the wild type PML and RARalpha proteins. Tretinoin 32-55 PML nuclear body scaffold Homo sapiens 218-221 15234573-0 2004 Alteration in the cellular response to retinoic acid of a human acute promyelocytic leukemia cell line, UF-1, carrying a patient-derived mutant PML-RARalpha chimeric gene. Tretinoin 39-52 PML nuclear body scaffold Homo sapiens 144-147 15234573-1 2004 Cellular response to all-trans retinoic acid (ATRA) of acute promyelocytic leukemia (APL) with patient-derived mutant PML-retinoic acid receptor-alpha (PML-RARalpha) was investigated using an APL cell line, UF-1, carrying Arg611Trp mutation in PML-RARalpha. Tretinoin 31-44 PML nuclear body scaffold Homo sapiens 118-121 15234573-1 2004 Cellular response to all-trans retinoic acid (ATRA) of acute promyelocytic leukemia (APL) with patient-derived mutant PML-retinoic acid receptor-alpha (PML-RARalpha) was investigated using an APL cell line, UF-1, carrying Arg611Trp mutation in PML-RARalpha. Tretinoin 31-44 PML nuclear body scaffold Homo sapiens 152-155 15234573-1 2004 Cellular response to all-trans retinoic acid (ATRA) of acute promyelocytic leukemia (APL) with patient-derived mutant PML-retinoic acid receptor-alpha (PML-RARalpha) was investigated using an APL cell line, UF-1, carrying Arg611Trp mutation in PML-RARalpha. Tretinoin 31-44 PML nuclear body scaffold Homo sapiens 152-155 15234573-1 2004 Cellular response to all-trans retinoic acid (ATRA) of acute promyelocytic leukemia (APL) with patient-derived mutant PML-retinoic acid receptor-alpha (PML-RARalpha) was investigated using an APL cell line, UF-1, carrying Arg611Trp mutation in PML-RARalpha. Tretinoin 46-50 PML nuclear body scaffold Homo sapiens 118-121 15234573-1 2004 Cellular response to all-trans retinoic acid (ATRA) of acute promyelocytic leukemia (APL) with patient-derived mutant PML-retinoic acid receptor-alpha (PML-RARalpha) was investigated using an APL cell line, UF-1, carrying Arg611Trp mutation in PML-RARalpha. Tretinoin 46-50 PML nuclear body scaffold Homo sapiens 152-155 15234573-1 2004 Cellular response to all-trans retinoic acid (ATRA) of acute promyelocytic leukemia (APL) with patient-derived mutant PML-retinoic acid receptor-alpha (PML-RARalpha) was investigated using an APL cell line, UF-1, carrying Arg611Trp mutation in PML-RARalpha. Tretinoin 46-50 PML nuclear body scaffold Homo sapiens 152-155 15160934-4 2004 The mechanism of action of both ATRA and As2O3 appears to be by inducing granulocytic differentiation and this cellular differentiation seems to depend on PML-RARalpha proteolysis. Tretinoin 32-36 PML nuclear body scaffold Homo sapiens 155-158 15218975-0 2004 Tetraploid acute promyelocytic leukemia with double PML/RARA gene rearrangements successfully treated with all-trans retinoic acid. Tretinoin 117-130 PML nuclear body scaffold Homo sapiens 52-55 14976428-4 2004 We proposed that C/EBPbeta is an ATRA-dependent PML/RARA target gene and that its activation is critical during ATRA-induced differentiation of APL cells. Tretinoin 33-37 PML nuclear body scaffold Homo sapiens 48-51 15103387-3 2004 PML/RARalpha is the central leukemia-inducing lesion in APL and is directly targeted by all trans retinoic acid (t-RA) as well as by arsenic, both compounds able to induce complete remissions. Tretinoin 92-111 PML nuclear body scaffold Homo sapiens 0-3 15103387-3 2004 PML/RARalpha is the central leukemia-inducing lesion in APL and is directly targeted by all trans retinoic acid (t-RA) as well as by arsenic, both compounds able to induce complete remissions. Tretinoin 113-117 PML nuclear body scaffold Homo sapiens 0-3 15116119-7 2004 This was associated with a right-shift and sharpening of the ATRA-induced maturation response compared to ATRA-sensitive NB4 cells, which corresponded to the transcriptional activation by PML-RARalphaPro900Ser of a cotransfected ATRA-targeted reporter vector in COS-1 cells. Tretinoin 61-65 PML nuclear body scaffold Homo sapiens 188-191 15116119-7 2004 This was associated with a right-shift and sharpening of the ATRA-induced maturation response compared to ATRA-sensitive NB4 cells, which corresponded to the transcriptional activation by PML-RARalphaPro900Ser of a cotransfected ATRA-targeted reporter vector in COS-1 cells. Tretinoin 106-110 PML nuclear body scaffold Homo sapiens 188-191 14976209-1 2004 Acute promyelocytic leukemia (APL) cases expressing the t(15,17) product, promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARalpha), have clinical remissions through leukemic cell differentiation after all-trans-retinoic acid (RA) treatment. Tretinoin 217-236 PML nuclear body scaffold Homo sapiens 98-101 15160934-5 2004 ATRA treatment results in partial cleavage and complete degradation of PML-RARalpha protein in differentiation sensitive, but not in differentiation resistant APL cells. Tretinoin 0-4 PML nuclear body scaffold Homo sapiens 71-74 15160934-8 2004 Therefore, PML-RARalpha proteolysis induced by ATRA and As2O3 may play an important role in overcoming the repressive activity of PML-RARalpha and allowing cellular differentiation to proceed. Tretinoin 47-51 PML nuclear body scaffold Homo sapiens 11-14 15160934-8 2004 Therefore, PML-RARalpha proteolysis induced by ATRA and As2O3 may play an important role in overcoming the repressive activity of PML-RARalpha and allowing cellular differentiation to proceed. Tretinoin 47-51 PML nuclear body scaffold Homo sapiens 130-133 15124139-5 2004 The majority of patients with promyelocytic leukemia with the PML/RARalpha fusion gene can be cured with an all-trans-retinoic acid and anthracycline-based treatment program. Tretinoin 108-131 PML nuclear body scaffold Homo sapiens 62-65 14630830-1 2004 The promyelocytic leukemia (PML) tumor suppressor of acute promyelocytic leukemia (APL) is essential for a number of proapoptotic and growth-suppressive pathways as well as for the activity of differentiating agents such as retinoic acid (RA). Tretinoin 224-237 PML nuclear body scaffold Homo sapiens 4-27 15160908-0 2004 Clinico-biological features and prognostic significance of PML/RARalpha isoforms in adult patients with acute promyelocytic leukemia treated with all trans retinoic acid (ATRA) and chemotherapy. Tretinoin 171-175 PML nuclear body scaffold Homo sapiens 59-62 14630830-1 2004 The promyelocytic leukemia (PML) tumor suppressor of acute promyelocytic leukemia (APL) is essential for a number of proapoptotic and growth-suppressive pathways as well as for the activity of differentiating agents such as retinoic acid (RA). Tretinoin 239-241 PML nuclear body scaffold Homo sapiens 4-27 14630830-6 2004 Complete functional loss of PML is therefore selected by the APL phenotype and associates with poor prognosis and RA unresponsiveness. Tretinoin 114-116 PML nuclear body scaffold Homo sapiens 28-31 15179005-8 2004 In PML-RARA-positive APL about 70% of patients are expected to be cured with a combination of ATRA and anthracycline-based chemotherapy. Tretinoin 94-98 PML nuclear body scaffold Homo sapiens 3-6 14871822-0 2004 Restoration of promyelocytic leukemia protein-nuclear bodies in neuroblastoma cells enhances retinoic acid responsiveness. Tretinoin 93-106 PML nuclear body scaffold Homo sapiens 15-45 14871822-6 2004 Expression of PML in neuroblastoma cells restored PML-nuclear bodies, enhanced responsiveness to all-trans-retinoic acid, and induced cellular differentiation. Tretinoin 97-120 PML nuclear body scaffold Homo sapiens 14-17 15160908-0 2004 Clinico-biological features and prognostic significance of PML/RARalpha isoforms in adult patients with acute promyelocytic leukemia treated with all trans retinoic acid (ATRA) and chemotherapy. Tretinoin 156-169 PML nuclear body scaffold Homo sapiens 59-62 14706140-1 2003 Detection of the PML/RARalpha fusion gene by RT-PCR in acute promyelocytic leukemia (APL) blasts is not only critical to commence promptly the specific therapy with all-trans retinoic acid (ATRA) or arsenic trioxide (As(2)O(3)), but also essential for the definition of PML breakpoint type and subsequent monitoring of minimal residual disease (MRD). Tretinoin 175-188 PML nuclear body scaffold Homo sapiens 17-20 14706140-1 2003 Detection of the PML/RARalpha fusion gene by RT-PCR in acute promyelocytic leukemia (APL) blasts is not only critical to commence promptly the specific therapy with all-trans retinoic acid (ATRA) or arsenic trioxide (As(2)O(3)), but also essential for the definition of PML breakpoint type and subsequent monitoring of minimal residual disease (MRD). Tretinoin 190-194 PML nuclear body scaffold Homo sapiens 17-20 14706140-1 2003 Detection of the PML/RARalpha fusion gene by RT-PCR in acute promyelocytic leukemia (APL) blasts is not only critical to commence promptly the specific therapy with all-trans retinoic acid (ATRA) or arsenic trioxide (As(2)O(3)), but also essential for the definition of PML breakpoint type and subsequent monitoring of minimal residual disease (MRD). Tretinoin 190-194 PML nuclear body scaffold Homo sapiens 270-273 12821942-1 2003 PML-RARalpha protein, the leukemogenic product of t(15,17) in acute promyelocytic leukemia, is cleaved into a truncated form termed deltaPML-RARalpha during all-trans retinoic acid (ATRA)-induced differentiation of NB4 cells. Tretinoin 167-180 PML nuclear body scaffold Homo sapiens 0-3 12893766-0 2003 Comparative analysis of genes regulated by PML/RAR alpha and PLZF/RAR alpha in response to retinoic acid using oligonucleotide arrays. Tretinoin 91-104 PML nuclear body scaffold Homo sapiens 43-56 14597990-8 2003 Interestingly, this PML/RARalpha-mediated increase in TF promoter activity is sensitive to ATRA treatment. Tretinoin 91-95 PML nuclear body scaffold Homo sapiens 20-23 14597990-9 2003 These data indicate that TF expression in APL cells is exacerbated by the presence of the PML/RARalpha fusion protein, and implicates the loss of Fos/Jun binding to the TF promoter in ATRA-induced suppression of TF. Tretinoin 184-188 PML nuclear body scaffold Homo sapiens 90-93 27265573-4 2003 ATRA-induced differentiation of APL cells is strictly dependent on the presence of PML-RAR alpha. Tretinoin 0-4 PML nuclear body scaffold Homo sapiens 83-86 12895391-2 2003 Reverse-transcription polymerase chain reaction (RT-PCR) amplification of PML-RARalpha messenger RNA can establish the diagnosis of APL, predict response to all-trans retinoic acid and arsenic trioxide, detect minimal residual disease, and predict relapse. Tretinoin 167-180 PML nuclear body scaffold Homo sapiens 74-77 12970771-5 2003 Treatment with pharmacological RA dosages overcomes the dominant-negative effects of PML/RARalpha to activate transcription of retinoid target genes. Tretinoin 31-33 PML nuclear body scaffold Homo sapiens 85-88 12970771-6 2003 This regulation is linked directly to RA effects in APL, including PML/RARalpha degradation and induction of differentiation. Tretinoin 38-40 PML nuclear body scaffold Homo sapiens 67-70 12821942-1 2003 PML-RARalpha protein, the leukemogenic product of t(15,17) in acute promyelocytic leukemia, is cleaved into a truncated form termed deltaPML-RARalpha during all-trans retinoic acid (ATRA)-induced differentiation of NB4 cells. Tretinoin 182-186 PML nuclear body scaffold Homo sapiens 0-3 12821942-4 2003 Treatment with hexamethylene bisacetamide (HMBA) combined with ATRA enhances ATRA-induced differentiation in ATRA-insensitive NB4-CI and arsenic-resistant NB4/As cells, and is associated with stabilization of PML-RARalpha protein and increased deltaPML-RARalpha formation. Tretinoin 63-67 PML nuclear body scaffold Homo sapiens 209-212 12821942-8 2003 These data suggest that (a) ATRA treatment induces PML-RARalpha cleavage by induction of unknown enzymes independent of proteasome- and caspase-mediated pathways; (b) deltaPML-RARalpha might function differently from both PML-RARalpha and RARalpha; (c) failure to cleave PML-RARalpha and form deltaPML-RARalpha after ATRA treatment may contribute to ATRA resistance in APL cells. Tretinoin 28-32 PML nuclear body scaffold Homo sapiens 51-54 12821942-8 2003 These data suggest that (a) ATRA treatment induces PML-RARalpha cleavage by induction of unknown enzymes independent of proteasome- and caspase-mediated pathways; (b) deltaPML-RARalpha might function differently from both PML-RARalpha and RARalpha; (c) failure to cleave PML-RARalpha and form deltaPML-RARalpha after ATRA treatment may contribute to ATRA resistance in APL cells. Tretinoin 28-32 PML nuclear body scaffold Homo sapiens 172-175 12821942-8 2003 These data suggest that (a) ATRA treatment induces PML-RARalpha cleavage by induction of unknown enzymes independent of proteasome- and caspase-mediated pathways; (b) deltaPML-RARalpha might function differently from both PML-RARalpha and RARalpha; (c) failure to cleave PML-RARalpha and form deltaPML-RARalpha after ATRA treatment may contribute to ATRA resistance in APL cells. Tretinoin 28-32 PML nuclear body scaffold Homo sapiens 172-175 12821942-8 2003 These data suggest that (a) ATRA treatment induces PML-RARalpha cleavage by induction of unknown enzymes independent of proteasome- and caspase-mediated pathways; (b) deltaPML-RARalpha might function differently from both PML-RARalpha and RARalpha; (c) failure to cleave PML-RARalpha and form deltaPML-RARalpha after ATRA treatment may contribute to ATRA resistance in APL cells. Tretinoin 317-321 PML nuclear body scaffold Homo sapiens 51-54 12773567-8 2003 All-trans-retinoic acid induced reorganization of the PML nuclear body (NB) and reappearance of the IR-induced TopBP1 foci. Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 54-57 12642121-6 2003 Standard protocols involving ATRA combined with anthracycline-based chemotherapy, lead to cure of approximately 70% patients with PML-RARalpha-associated APL. Tretinoin 29-33 PML nuclear body scaffold Homo sapiens 130-133 11891284-1 2002 All-trans-retinoic acid (RA) treatment induces remissions in acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, promyelocytic leukemia (PML)/RA receptor alpha (RARalpha). Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 159-162 12769347-10 2003 The results suggest that while in normal hematopoietic cells and in PML CD34 - cells induction of CD38 antigen expression by RA results in terminal differentiation along the myeloid lineage, in early myeloblastic leukemic CD34 + cells, induction of CD38 and differentiation are not functionally related. Tretinoin 125-127 PML nuclear body scaffold Homo sapiens 68-71 12647219-3 2003 The expression of PML, revealed as speckled or microgranular staining in the nuclei, was positively correlated with the differentiation status of NB cells in vivo, and was upregulated during the differentiation of KCNR and SY5Y cells following retinoic acid treatment. Tretinoin 244-257 PML nuclear body scaffold Homo sapiens 18-21 12239173-0 2002 Response to histone deacetylase inhibition of novel PML/RARalpha mutants detected in retinoic acid-resistant APL cells. Tretinoin 85-98 PML nuclear body scaffold Homo sapiens 52-55 12239173-7 2002 Cotreatment with ATRA and TSA restored RARbeta gene expression in NB4-MRA1 cells, whose PML/RARalpha mutation is in helix 12 of the LBD, but not in an APL cell line harboring the patient-derived PML/RARalpha mutation, which was between helix 5 and 6. Tretinoin 17-21 PML nuclear body scaffold Homo sapiens 88-91 12239173-7 2002 Cotreatment with ATRA and TSA restored RARbeta gene expression in NB4-MRA1 cells, whose PML/RARalpha mutation is in helix 12 of the LBD, but not in an APL cell line harboring the patient-derived PML/RARalpha mutation, which was between helix 5 and 6. Tretinoin 17-21 PML nuclear body scaffold Homo sapiens 195-198 12357342-3 2002 The treatment of APL patients with all-trans retinoic acid (ATRA) results in clinical remission associated with blast cell differentiation and reformation of the PML nuclear bodies. Tretinoin 39-58 PML nuclear body scaffold Homo sapiens 162-165 12357342-3 2002 The treatment of APL patients with all-trans retinoic acid (ATRA) results in clinical remission associated with blast cell differentiation and reformation of the PML nuclear bodies. Tretinoin 60-64 PML nuclear body scaffold Homo sapiens 162-165 12357343-5 2002 According to this idea the PML-RARalpha fusion protein promotes leukemogenesis not only through repression of retinoic acid responsive genes, but also by way of interfering with several tumor suppressor proteins that cooperate to establish senescence. Tretinoin 110-123 PML nuclear body scaffold Homo sapiens 27-30 12357345-5 2002 It is also likely that treatment of APL cells by retinoic acid induces de novo up-regulation of the same genes which are dominantly repressed by PML-RARalpha and whose expression is required for reactivation of the differentiation program. Tretinoin 49-62 PML nuclear body scaffold Homo sapiens 145-148 11788605-7 2002 Luciferase activity in transformed cells markedly increased in response to ATRA stimulation when the wild type RARalpha or the PML/RARalpha hybrid protein was co-expressed. Tretinoin 75-79 PML nuclear body scaffold Homo sapiens 127-130 12032336-0 2002 Variant-type PML-RAR(alpha) fusion transcript in acute promyelocytic leukemia: use of a cryptic coding sequence from intron 2 of the RAR(alpha) gene and identification of a new clinical subtype resistant to retinoic acid therapy. Tretinoin 207-220 PML nuclear body scaffold Homo sapiens 13-16 12032336-10 2002 In these cases, the aberrant V-type PML-RAR(alpha) protein displayed increased affinity to the nuclear corepressor protein SMRT, providing further evidence that RA exerts the therapeutic effect on APL through modulation of the RAR-corepressor interaction. Tretinoin 40-42 PML nuclear body scaffold Homo sapiens 36-39 11891284-1 2002 All-trans-retinoic acid (RA) treatment induces remissions in acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, promyelocytic leukemia (PML)/RA receptor alpha (RARalpha). Tretinoin 25-27 PML nuclear body scaffold Homo sapiens 159-162 11930660-11 2002 This implies that there may be a pathway other than PML/RAR alpha fusion gene product which mediates ATRA-induced myeloid maturation in leukemia cells. Tretinoin 101-105 PML nuclear body scaffold Homo sapiens 52-65 11830487-1 2002 This study identified missense mutations in the ligand binding domain of the oncoprotein PML-RARalpha in 5 of 8 patients with acute promyelocytic leukemia (APL) with 2 or more relapses and 2 or more previous courses of all-trans retinoic acid (RA)-containing therapy. Tretinoin 229-242 PML nuclear body scaffold Homo sapiens 89-92 11830487-1 2002 This study identified missense mutations in the ligand binding domain of the oncoprotein PML-RARalpha in 5 of 8 patients with acute promyelocytic leukemia (APL) with 2 or more relapses and 2 or more previous courses of all-trans retinoic acid (RA)-containing therapy. Tretinoin 93-95 PML nuclear body scaffold Homo sapiens 89-92 11830487-4 2002 Of the 5 RA + PB-treated patients, 4 had PML-RARalpha mutations. Tretinoin 9-11 PML nuclear body scaffold Homo sapiens 41-44 11830487-5 2002 The Gly289Arg mutation in the clinical responder produced the most defective PML-RARalpha function in the presence of RA with or without sodium butyrate (NaB) or trichostatin A. Tretinoin 81-83 PML nuclear body scaffold Homo sapiens 77-80 11830487-8 2002 These results indicate that PML-RARalpha mutations occurred with high frequency after multiple RA treatment relapses, indicate that the functional potential of PML-RARalpha was not correlated with clinical response to RA + PB treatment, and suggest that the response to RA + PB therapy in one patient was related to the ability of PB to circumvent the blocked RA-regulated gene response pathway. Tretinoin 32-34 PML nuclear body scaffold Homo sapiens 28-31 11830487-8 2002 These results indicate that PML-RARalpha mutations occurred with high frequency after multiple RA treatment relapses, indicate that the functional potential of PML-RARalpha was not correlated with clinical response to RA + PB treatment, and suggest that the response to RA + PB therapy in one patient was related to the ability of PB to circumvent the blocked RA-regulated gene response pathway. Tretinoin 95-97 PML nuclear body scaffold Homo sapiens 28-31 11830487-8 2002 These results indicate that PML-RARalpha mutations occurred with high frequency after multiple RA treatment relapses, indicate that the functional potential of PML-RARalpha was not correlated with clinical response to RA + PB treatment, and suggest that the response to RA + PB therapy in one patient was related to the ability of PB to circumvent the blocked RA-regulated gene response pathway. Tretinoin 95-97 PML nuclear body scaffold Homo sapiens 28-31 11830487-8 2002 These results indicate that PML-RARalpha mutations occurred with high frequency after multiple RA treatment relapses, indicate that the functional potential of PML-RARalpha was not correlated with clinical response to RA + PB treatment, and suggest that the response to RA + PB therapy in one patient was related to the ability of PB to circumvent the blocked RA-regulated gene response pathway. Tretinoin 95-97 PML nuclear body scaffold Homo sapiens 28-31 12015078-5 2002 (2) After treatment with ATRA, the fusion protein disappeared and PML protein resumed in NB4 cells, while in HL-60 and K562 cells there was no difference from control cells. Tretinoin 25-29 PML nuclear body scaffold Homo sapiens 66-69 11682484-1 2002 In acute promyelocytic leukemia (APL) cells harboring the promyelocytic leukemia retinoic acid receptor alpha (PML-RARalpha) chimeric protein, retinoic acid (RA)-induced differentiation is triggered through a PML-RARalpha signaling resulting in activation of critical target genes. Tretinoin 81-94 PML nuclear body scaffold Homo sapiens 111-114 11682484-1 2002 In acute promyelocytic leukemia (APL) cells harboring the promyelocytic leukemia retinoic acid receptor alpha (PML-RARalpha) chimeric protein, retinoic acid (RA)-induced differentiation is triggered through a PML-RARalpha signaling resulting in activation of critical target genes. Tretinoin 115-117 PML nuclear body scaffold Homo sapiens 111-114 11682484-4 2002 PML-RARalpha strongly enhanced RA-induced ASB-2 mRNA expression. Tretinoin 4-6 PML nuclear body scaffold Homo sapiens 0-3 11818666-1 2002 The presence of the characteristic fusion transcript gene, promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARalpha), provided hematologists with a rationale for the use of all-trans retinoic acid (ATRA) for differentiation therapy for acute promyelocytic leukemia (APL). Tretinoin 182-205 PML nuclear body scaffold Homo sapiens 112-115 11818666-1 2002 The presence of the characteristic fusion transcript gene, promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARalpha), provided hematologists with a rationale for the use of all-trans retinoic acid (ATRA) for differentiation therapy for acute promyelocytic leukemia (APL). Tretinoin 207-211 PML nuclear body scaffold Homo sapiens 112-115 11779431-7 2001 Both ATRA and As2O3 can also down-regulate the TF antigen in U937 cells transfected with or without PML-RARa. Tretinoin 5-9 PML nuclear body scaffold Homo sapiens 100-103 11704843-5 2001 The effect of As(2)O(3) has been shown to be related to the expression of APL-specific PML-RARalpha oncoprotein, and there is a synergistic effect between As(2)O(3) and ATRA in an APL mouse model. Tretinoin 169-173 PML nuclear body scaffold Homo sapiens 87-90 11704854-0 2001 Pathways of retinoic acid- or arsenic trioxide-induced PML/RARalpha catabolism, role of oncogene degradation in disease remission. Tretinoin 12-25 PML nuclear body scaffold Homo sapiens 55-58 11301322-0 2001 PRAM-1 is a novel adaptor protein regulated by retinoic acid (RA) and promyelocytic leukemia (PML)-RA receptor alpha in acute promyelocytic leukemia cells. Tretinoin 1-3 PML nuclear body scaffold Homo sapiens 70-92 11301322-0 2001 PRAM-1 is a novel adaptor protein regulated by retinoic acid (RA) and promyelocytic leukemia (PML)-RA receptor alpha in acute promyelocytic leukemia cells. Tretinoin 1-3 PML nuclear body scaffold Homo sapiens 94-97 11301322-2 2001 Complete remission of acute promyelocytic leukemia can be obtained by treating patients with all-trans retinoic acid, and PML-RARalpha plays a major role in mediating retinoic acid effects in leukemia cells. Tretinoin 167-180 PML nuclear body scaffold Homo sapiens 122-125 11301322-4 2001 By applying subtraction cloning to acute promyelocytic leukemia cells, we identified a retinoic acid-induced gene, PRAM-1 (PML-RARalpha target gene encoding an Adaptor Molecule-1), which encodes a novel adaptor protein sharing structural homologies with the SLAP-130/fyb adaptor. Tretinoin 87-100 PML nuclear body scaffold Homo sapiens 41-63 11301322-4 2001 By applying subtraction cloning to acute promyelocytic leukemia cells, we identified a retinoic acid-induced gene, PRAM-1 (PML-RARalpha target gene encoding an Adaptor Molecule-1), which encodes a novel adaptor protein sharing structural homologies with the SLAP-130/fyb adaptor. Tretinoin 87-100 PML nuclear body scaffold Homo sapiens 123-126 11301322-8 2001 By providing the first evidence that PML-RARalpha dysregulates expression of an adaptor protein, our data open new insights into signaling events that are disrupted during transformation by PML-RARalpha and induced by retinoic acid during de novo differentiation of acute promyelocytic leukemia cells. Tretinoin 218-231 PML nuclear body scaffold Homo sapiens 37-40 11699203-0 2001 Acute promyelocytic leukemia with apparently normal karyotype: molecular findings and response to all-trans retinoic acid. Tretinoin 108-121 PML nuclear body scaffold Homo sapiens 6-28 11699203-7 2001 The present study shows the key role of the fusion of PML-RARA in the responsiveness to ATRA as well as in the leukemogenesis of APL. Tretinoin 88-92 PML nuclear body scaffold Homo sapiens 54-57 11342454-0 2001 Tyrosine kinase inhibitor STI571 potentiates the pharmacologic activity of retinoic acid in acute promyelocytic leukemia cells: effects on the degradation of RARalpha and PML-RARalpha. Tretinoin 75-88 PML nuclear body scaffold Homo sapiens 171-174 11264371-6 2001 After treatment with retinoic acid, NT2 cells differentiate into neuron-like hNT cells which express very high levels of both PML and Sp100. Tretinoin 21-34 PML nuclear body scaffold Homo sapiens 126-129 11681409-0 2001 Pulsed ATRA as single therapy restores long-term remission in PML-RARalpha-positive acute promyelocytic leukemia patients: real time quantification of minimal residual disease. Tretinoin 7-11 PML nuclear body scaffold Homo sapiens 62-65 11438209-0 2001 Novel mutation in the PML/RARalpha chimeric gene exhibits dramatically decreased ligand-binding activity and confers acquired resistance to retinoic acid in acute promyelocytic leukemia. Tretinoin 140-153 PML nuclear body scaffold Homo sapiens 22-25 11438209-9 2001 Interestingly, RA-binding activity was dramatically decreased in the mutant PML/RARalpha compared with that of the wild-type chimeric protein, suggesting that this single amino acid substitution is critical for RA binding. Tretinoin 15-17 PML nuclear body scaffold Homo sapiens 76-79 11438209-9 2001 Interestingly, RA-binding activity was dramatically decreased in the mutant PML/RARalpha compared with that of the wild-type chimeric protein, suggesting that this single amino acid substitution is critical for RA binding. Tretinoin 80-82 PML nuclear body scaffold Homo sapiens 76-79 11438209-11 2001 We conclude that acquisition of the PML/RARalpha mutation is one possible mechanism for development of RA resistance in patients with APL in vivo. Tretinoin 40-42 PML nuclear body scaffold Homo sapiens 36-39 11133770-1 2001 All-trans retinoic acid (tRA) and arsenic trioxide (As(2)O(3)) induce non-cross-resistant complete clinical remission in patients with acute promyelocytic leukemia with t(15;17) translocation and target PML-RARalpha, the leukemogenic protein, by different pathways suggesting a possible therapeutic synergism. Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 203-206 11133770-1 2001 All-trans retinoic acid (tRA) and arsenic trioxide (As(2)O(3)) induce non-cross-resistant complete clinical remission in patients with acute promyelocytic leukemia with t(15;17) translocation and target PML-RARalpha, the leukemogenic protein, by different pathways suggesting a possible therapeutic synergism. Tretinoin 25-28 PML nuclear body scaffold Homo sapiens 203-206 27419349-0 2001 Exogenous PML/RARalpha Fusion Gene Responds to All-trans Retinoic Acid Results in Differentiation of the Human B Cell Line. Tretinoin 57-70 PML nuclear body scaffold Homo sapiens 10-13 27419349-1 2001 The interaction of an exogenous PML/RARalpha fusion gene, associated with acute promyelocytic leukemia, with all-trans retinoic acid (ATRA) was examined in B-lymphoid cell lines. Tretinoin 119-132 PML nuclear body scaffold Homo sapiens 32-35 27419349-1 2001 The interaction of an exogenous PML/RARalpha fusion gene, associated with acute promyelocytic leukemia, with all-trans retinoic acid (ATRA) was examined in B-lymphoid cell lines. Tretinoin 134-138 PML nuclear body scaffold Homo sapiens 32-35 11050004-0 2000 Altered ligand binding and transcriptional regulation by mutations in the PML/RARalpha ligand-binding domain arising in retinoic acid-resistant patients with acute promyelocytic leukemia. Tretinoin 120-133 PML nuclear body scaffold Homo sapiens 74-77 27419349-5 2001 When these results are taken together, it can be observed that the exogenous PML/RARalpha fusion gene responds to ATRA, which results in cell differentiation of the human B cell line. Tretinoin 114-118 PML nuclear body scaffold Homo sapiens 77-80 11007958-3 2000 At the molecular level, PML protein has been shown to be a coactivator of nuclear hormone receptors, whereas its oncogenic counterpart PML-retinoic acid receptor alpha, which promotes POD disaggregation, has been found to activate activator protein-1 transcription in a retinoic acid-dependent manner. Tretinoin 139-152 PML nuclear body scaffold Homo sapiens 135-138 11112687-6 2001 Moreover, retinoic acid treatment, which causes remission of APL in patients and reformation of PML-containing bodies in NB4 cells, relocalized PA28 to this site. Tretinoin 10-23 PML nuclear body scaffold Homo sapiens 96-99 11050004-4 2000 Recently, mutations in PML/RARalpha have been described in APL cells from patients clinically resistant to RA therapy. Tretinoin 27-29 PML nuclear body scaffold Homo sapiens 23-26 10870476-4 2000 In the presence of high levels of all-trans retinoic acid (ATRA), both PML-dependent apoptotic mechanisms and myeloid-specific gene expression programs are reactivated. Tretinoin 44-57 PML nuclear body scaffold Homo sapiens 71-74 10865965-16 2000 We conclude that (1) ATRA combined to EMA chemotherapy is effective in the treatment of relapsed APL; (2) allogeneic BMT may be too toxic after salvage treatment including EMA intensive chemotherapy; (3) clinical outcome of autografted patients and preliminary molecular results regarding detection of PML/RARalpha after autologous PBSCT are encouraging. Tretinoin 21-25 PML nuclear body scaffold Homo sapiens 302-305 10870476-4 2000 In the presence of high levels of all-trans retinoic acid (ATRA), both PML-dependent apoptotic mechanisms and myeloid-specific gene expression programs are reactivated. Tretinoin 59-63 PML nuclear body scaffold Homo sapiens 71-74 10373566-2 1999 APLs with PML-RARalpha or PLZF-RARalpha fusion protein differ only in their response to retinoic acid (RA) treatment: the t(15;17) (PML-RARalpha-positive) APL blasts are sensitive to RA in vitro, and patients enter disease remission after RA treatment, while those with t(11;17) (PLZF-RARalpha-positive) APLs do not. Tretinoin 88-101 PML nuclear body scaffold Homo sapiens 10-13 10766166-2 2000 The purpose of this study was to identify genes that are regulated in a PML-RARalpha-dependent fashion by retinoic acid (RA), because such genes may be integrally involved in APL pathogenesis and/or myeloid differentiation. Tretinoin 106-119 PML nuclear body scaffold Homo sapiens 72-75 10766166-2 2000 The purpose of this study was to identify genes that are regulated in a PML-RARalpha-dependent fashion by retinoic acid (RA), because such genes may be integrally involved in APL pathogenesis and/or myeloid differentiation. Tretinoin 76-78 PML nuclear body scaffold Homo sapiens 72-75 10766166-7 2000 B94 was also induced by RA in NB4, UF1, and HL-60 cells, but not in other hematopoietic cell lines tested, suggesting that its up-regulation by RA may be specific to cells that express PML-RARalpha or are at the late myeloblast or promyelocyte stage of myeloid development. Tretinoin 144-146 PML nuclear body scaffold Homo sapiens 185-188 10673742-1 2000 The fusion protein PML/RARA, associated with acute promyelocytic leukemia behaves as an abnormal retinoic acid (RA) receptor with altered transactivation properties but is still inducible by RA. Tretinoin 23-25 PML nuclear body scaffold Homo sapiens 19-22 10673742-3 2000 This has been supported by works reporting that in vitro ATRA resistance is characterized by defects in the RARA/E-domain of PML/RARA. Tretinoin 57-61 PML nuclear body scaffold Homo sapiens 125-128 10673742-4 2000 In the present report, we identified a new mutation in the E domain of PML/RARA which is associated with a RA-resistant subline of NB4 cells; NB4-R2. Tretinoin 75-77 PML nuclear body scaffold Homo sapiens 71-74 10637480-2 2000 The difference in response to ATRA therapy between acute promyelocytic leukemia (APL) patients with PML-RARalpha fusion and PLZF-RARalpha fusion has recently been found to be partially due to the strong association of the transcriptional co-repressor, SMRT/N-CoR, with PLZF domain. Tretinoin 30-34 PML nuclear body scaffold Homo sapiens 100-104 10637480-3 2000 We demonstrate that SMRT association, as with PML-RARalpha, can be released from NPM-RARalpha at pharmacological concentration of ATRA (10-6 M). Tretinoin 130-134 PML nuclear body scaffold Homo sapiens 46-50 10611294-1 1999 Analyzing the pathways by which retinoic acid (RA) induces promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha) catabolism in acute promyelocytic leukemia (APL), we found that, in addition to caspase-mediated PML/RARalpha cleavage, RA triggers degradation of both PML/RARalpha and RARalpha. Tretinoin 32-45 PML nuclear body scaffold Homo sapiens 112-115 10611294-1 1999 Analyzing the pathways by which retinoic acid (RA) induces promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha) catabolism in acute promyelocytic leukemia (APL), we found that, in addition to caspase-mediated PML/RARalpha cleavage, RA triggers degradation of both PML/RARalpha and RARalpha. Tretinoin 32-45 PML nuclear body scaffold Homo sapiens 223-226 10611294-1 1999 Analyzing the pathways by which retinoic acid (RA) induces promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha) catabolism in acute promyelocytic leukemia (APL), we found that, in addition to caspase-mediated PML/RARalpha cleavage, RA triggers degradation of both PML/RARalpha and RARalpha. Tretinoin 32-45 PML nuclear body scaffold Homo sapiens 223-226 10611294-1 1999 Analyzing the pathways by which retinoic acid (RA) induces promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha) catabolism in acute promyelocytic leukemia (APL), we found that, in addition to caspase-mediated PML/RARalpha cleavage, RA triggers degradation of both PML/RARalpha and RARalpha. Tretinoin 47-49 PML nuclear body scaffold Homo sapiens 112-115 10611294-1 1999 Analyzing the pathways by which retinoic acid (RA) induces promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha) catabolism in acute promyelocytic leukemia (APL), we found that, in addition to caspase-mediated PML/RARalpha cleavage, RA triggers degradation of both PML/RARalpha and RARalpha. Tretinoin 47-49 PML nuclear body scaffold Homo sapiens 223-226 10611294-1 1999 Analyzing the pathways by which retinoic acid (RA) induces promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha) catabolism in acute promyelocytic leukemia (APL), we found that, in addition to caspase-mediated PML/RARalpha cleavage, RA triggers degradation of both PML/RARalpha and RARalpha. Tretinoin 47-49 PML nuclear body scaffold Homo sapiens 223-226 10539879-1 1999 The results of the treatment of 43 patients with acute promyelocytic leukemia (PML) are reported: 27 were treated initially with all-trans-retinoic acid (ATRA), whereas 16 were treated with conventional chemotherapy. Tretinoin 129-152 PML nuclear body scaffold Homo sapiens 79-82 10610177-2 1999 Here we show that PML, Tif1alpha and RXRalpha/RARalpha function together in a transcription complex that is dependent on retinoic acid (RA). Tretinoin 121-134 PML nuclear body scaffold Homo sapiens 18-21 10610177-2 1999 Here we show that PML, Tif1alpha and RXRalpha/RARalpha function together in a transcription complex that is dependent on retinoic acid (RA). Tretinoin 46-48 PML nuclear body scaffold Homo sapiens 18-21 10610177-7 1999 T18, similar to PML-RARalpha, disrupts the RA-dependent activity of this complex in a dominant-negative manner resulting in a growth advantage. Tretinoin 20-22 PML nuclear body scaffold Homo sapiens 16-19 10373566-2 1999 APLs with PML-RARalpha or PLZF-RARalpha fusion protein differ only in their response to retinoic acid (RA) treatment: the t(15;17) (PML-RARalpha-positive) APL blasts are sensitive to RA in vitro, and patients enter disease remission after RA treatment, while those with t(11;17) (PLZF-RARalpha-positive) APLs do not. Tretinoin 31-33 PML nuclear body scaffold Homo sapiens 132-135 10373566-2 1999 APLs with PML-RARalpha or PLZF-RARalpha fusion protein differ only in their response to retinoic acid (RA) treatment: the t(15;17) (PML-RARalpha-positive) APL blasts are sensitive to RA in vitro, and patients enter disease remission after RA treatment, while those with t(11;17) (PLZF-RARalpha-positive) APLs do not. Tretinoin 31-33 PML nuclear body scaffold Homo sapiens 132-135 10373566-3 1999 Recently it has been shown that complete remission can be achieved upon treatment with arsenic trioxide (As2O3) in PML-RARalpha-positive APL, even when the patient has relapsed and the disease is RA resistant. Tretinoin 119-121 PML nuclear body scaffold Homo sapiens 115-118 11798775-8 2000 1.0 micromol/L ATRA also exerted, to a less extent than As(2)O(3), growth-inhibitory effects in K(V) sublines, which became more obvious in K(PML) but not in K(PLZF) sublines. Tretinoin 15-19 PML nuclear body scaffold Homo sapiens 142-145 10702898-4 2000 The PML/RARa protein product is responsible for the leukemic phenotype in these patients, but is also able to respond to pharmacologic levels of retinoic acid and induce cell differentiation. Tretinoin 145-158 PML nuclear body scaffold Homo sapiens 4-7 10684855-7 2000 Upon retinoic acid treatment, which induces disease remission in APL, Daxx relocalizes to the PML NBs. Tretinoin 5-18 PML nuclear body scaffold Homo sapiens 94-97 11389537-5 2000 In t(15;17)-containing leukemic cells, the PML nuclear bodies are disrupted, but reform when the leukemic cells are induced to differentiate in the presence of all-trans retinoic acid. Tretinoin 170-183 PML nuclear body scaffold Homo sapiens 43-46 10597230-0 1999 Formation of PML/RAR alpha high molecular weight nuclear complexes through the PML coiled-coil region is essential for the PML/RAR alpha-mediated retinoic acid response. Tretinoin 146-159 PML nuclear body scaffold Homo sapiens 13-26 10597230-0 1999 Formation of PML/RAR alpha high molecular weight nuclear complexes through the PML coiled-coil region is essential for the PML/RAR alpha-mediated retinoic acid response. Tretinoin 146-159 PML nuclear body scaffold Homo sapiens 13-16 10597230-0 1999 Formation of PML/RAR alpha high molecular weight nuclear complexes through the PML coiled-coil region is essential for the PML/RAR alpha-mediated retinoic acid response. Tretinoin 146-159 PML nuclear body scaffold Homo sapiens 123-136 10597230-2 1999 RA-sensitivity in APL is mediated by its oncogenic protein, which results from the recombination of the PML and the RA receptor alpha (RAR alpha) genes (PML/RAR alpha fusion protein). Tretinoin 0-2 PML nuclear body scaffold Homo sapiens 104-107 10597230-2 1999 RA-sensitivity in APL is mediated by its oncogenic protein, which results from the recombination of the PML and the RA receptor alpha (RAR alpha) genes (PML/RAR alpha fusion protein). Tretinoin 0-2 PML nuclear body scaffold Homo sapiens 153-166 10553155-2 1999 All-trans retinoic acid probably induces differentiation of atypical promyelocytes and clinical remission in APL patients by binding to the ligand binding domain (LBD) of the RARa portion of the PML-RARa chimeric protein. Tretinoin 10-23 PML nuclear body scaffold Homo sapiens 195-198 10553155-3 1999 Structural alterations of the LBD of the PML/RARa have been revealed in ATRA-resistant APL cell lines and in a few APL patients with acquired clinical resistance to ATRA therapy. Tretinoin 72-76 PML nuclear body scaffold Homo sapiens 41-44 10553155-4 1999 Two APL relapsed patients with clinical resistance to ATRA therapy were evaluated for the presence of nucleotide mutations in the LBD of PML/RARa gene and then treated with arsenic trioxide (As2O3). Tretinoin 54-58 PML nuclear body scaffold Homo sapiens 137-140 10553155-8 1999 RESULTS: In both patients, at the ATRA-resistant relapse, a missense point mutation in the LBD of the PML/RARa gene was found. Tretinoin 34-38 PML nuclear body scaffold Homo sapiens 102-105 10439807-2 1999 Since treatment response to all-trans retinoic acid correlates directly with PML/RAR alpha, expeditious documentation is critical to patient care. Tretinoin 38-51 PML nuclear body scaffold Homo sapiens 77-90 10373566-2 1999 APLs with PML-RARalpha or PLZF-RARalpha fusion protein differ only in their response to retinoic acid (RA) treatment: the t(15;17) (PML-RARalpha-positive) APL blasts are sensitive to RA in vitro, and patients enter disease remission after RA treatment, while those with t(11;17) (PLZF-RARalpha-positive) APLs do not. Tretinoin 88-101 PML nuclear body scaffold Homo sapiens 132-135 10373566-2 1999 APLs with PML-RARalpha or PLZF-RARalpha fusion protein differ only in their response to retinoic acid (RA) treatment: the t(15;17) (PML-RARalpha-positive) APL blasts are sensitive to RA in vitro, and patients enter disease remission after RA treatment, while those with t(11;17) (PLZF-RARalpha-positive) APLs do not. Tretinoin 14-16 PML nuclear body scaffold Homo sapiens 10-13 10373566-2 1999 APLs with PML-RARalpha or PLZF-RARalpha fusion protein differ only in their response to retinoic acid (RA) treatment: the t(15;17) (PML-RARalpha-positive) APL blasts are sensitive to RA in vitro, and patients enter disease remission after RA treatment, while those with t(11;17) (PLZF-RARalpha-positive) APLs do not. Tretinoin 14-16 PML nuclear body scaffold Homo sapiens 132-135 10359529-5 1999 RA-treatment induced two peaks of p21 synthesis: early (from the 2nd to the 6th hour), dependent on PML/RAR alpha expression and associated with G1-S transition and high CDK activity; late (from 3rd to the 4th day), independent from PML/RAR alpha and associated with G1 block and low CDK activity. Tretinoin 0-2 PML nuclear body scaffold Homo sapiens 100-113 10359529-5 1999 RA-treatment induced two peaks of p21 synthesis: early (from the 2nd to the 6th hour), dependent on PML/RAR alpha expression and associated with G1-S transition and high CDK activity; late (from 3rd to the 4th day), independent from PML/RAR alpha and associated with G1 block and low CDK activity. Tretinoin 0-2 PML nuclear body scaffold Homo sapiens 233-246 10330422-5 1999 The RA-induced expression of C/EBPepsilon markedly increased in U937 myelomonoblasts that were induced to express promyelocytic leukemia/RARalpha (PML/RARalpha), but not in those induced to express promyelocytic leukemia zinc finger/RARalpha (PLZF/RARalpha). Tretinoin 4-6 PML nuclear body scaffold Homo sapiens 147-150 10203615-1 1999 We analyzed the efficacy of all-trans retinoic acid (ATRA) as an early treatment for four acute promyelocytic leukemia (APL) patients in remission who were PML/RARalpha-positive by reverse transcription-polymerase chain reaction or fluorescence in situ hybridization. Tretinoin 28-51 PML nuclear body scaffold Homo sapiens 156-159 10356361-4 1999 We showed in this study that PML/RARalpha increased the transcription of p21WAF1/CIP1 gene and the activation was further induced by RA treatment. Tretinoin 33-35 PML nuclear body scaffold Homo sapiens 29-32 10356361-7 1999 These results suggest that the induction of APL cells differentiation by RA may be a result of the activation of p21WAF1/CIP1 by PML/RARalpha. Tretinoin 73-75 PML nuclear body scaffold Homo sapiens 129-132 10203615-1 1999 We analyzed the efficacy of all-trans retinoic acid (ATRA) as an early treatment for four acute promyelocytic leukemia (APL) patients in remission who were PML/RARalpha-positive by reverse transcription-polymerase chain reaction or fluorescence in situ hybridization. Tretinoin 53-57 PML nuclear body scaffold Homo sapiens 156-159 10203615-7 1999 These findings suggest that early treatment of ATRA for PML/RARalpha-positive APL patients in remission may have a therapeutic benefit and prolong the duration of hematological remission without chemotherapy. Tretinoin 47-51 PML nuclear body scaffold Homo sapiens 56-59 10029573-0 1999 Constitutive degradation of PML/RARalpha through the proteasome pathway mediates retinoic acid resistance. Tretinoin 81-94 PML nuclear body scaffold Homo sapiens 28-31 10233384-6 1999 Similarly, blasts from this case were found to be sensitive to ATRA in vitro as determined by NBT reduction test and by normalization of the PML nuclear body staining pattern. Tretinoin 63-67 PML nuclear body scaffold Homo sapiens 141-144 10029573-2 1999 Treatment with retinoic acid (RA) induces degradation of PML/RARalpha, differentiation of leukaemic blasts, and disease remission. Tretinoin 15-28 PML nuclear body scaffold Homo sapiens 57-60 10029573-2 1999 Treatment with retinoic acid (RA) induces degradation of PML/RARalpha, differentiation of leukaemic blasts, and disease remission. Tretinoin 30-32 PML nuclear body scaffold Homo sapiens 57-60 10029573-8 1999 Similarly, forced expression of PML/RARalpha, but not RARalpha, into the NB4/007.6 cells restored sensitivity to RA treatment to levels comparable to those of the NB4 cells. Tretinoin 36-38 PML nuclear body scaffold Homo sapiens 32-35 9891864-10 1999 The demonstration that PML-RAR alpha is degraded, perhaps via a ubiquitin-dependent pathway, in response to ATRA. Tretinoin 108-112 PML nuclear body scaffold Homo sapiens 23-26 9716606-8 1998 Reducing PML/RARalpha protein in NB4-R1 cells rendered these cells more sensitive to ATRA. Tretinoin 85-89 PML nuclear body scaffold Homo sapiens 9-12 9778041-2 1998 PML/RAR alpha expression is linked to leukemogenesis and to clinical sensitivity to all-trans retinoic acid (RA). Tretinoin 94-107 PML nuclear body scaffold Homo sapiens 0-13 9746761-1 1998 All-trans-retinoic acid (RA) treatment induces morphological remission in acute promyelocytic leukemia (APL) patients carrying the t(15;17) and expressing the PML/RARalpha product by inducing terminal differentiation of the leukemic clone. Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 159-162 9746761-1 1998 All-trans-retinoic acid (RA) treatment induces morphological remission in acute promyelocytic leukemia (APL) patients carrying the t(15;17) and expressing the PML/RARalpha product by inducing terminal differentiation of the leukemic clone. Tretinoin 25-27 PML nuclear body scaffold Homo sapiens 159-162 9746761-2 1998 RA treatment induces downregulation of PML/RARalpha and reorganization of the PML-nuclear bodies. Tretinoin 0-2 PML nuclear body scaffold Homo sapiens 39-42 9746761-2 1998 RA treatment induces downregulation of PML/RARalpha and reorganization of the PML-nuclear bodies. Tretinoin 0-2 PML nuclear body scaffold Homo sapiens 78-81 9746761-4 1998 Here, we show that in the APL-derived NB4 cell line as well as in myeloid precursor U937 cells expressing the PML/RARalpha (U937/PR9) and in blasts from APL patients, the PML/RARalpha fusion protein is cleaved by a caspase 3-like activity induced by RA treatment. Tretinoin 114-116 PML nuclear body scaffold Homo sapiens 110-113 9746761-5 1998 In fact, a caspase 3-like activity is detectable in PML/RARalpha expressing cells after RA treatment, and selective caspase inhibitor peptides are able to prevent the RA-induced degradation of the fusion protein in vivo and in vitro. Tretinoin 56-58 PML nuclear body scaffold Homo sapiens 52-55 9746761-5 1998 In fact, a caspase 3-like activity is detectable in PML/RARalpha expressing cells after RA treatment, and selective caspase inhibitor peptides are able to prevent the RA-induced degradation of the fusion protein in vivo and in vitro. Tretinoin 88-90 PML nuclear body scaffold Homo sapiens 52-55 9746761-7 1998 The extent of PML/RARalpha cleavage directly correlates with the ability of RA to restore the normal PML nuclear bodies (NBs) pattern. Tretinoin 18-20 PML nuclear body scaffold Homo sapiens 101-104 9746761-9 1998 These results indicate that PML/RARalpha is directly involved in conferring RA sensitivity of APL cells and that the RA-induced reassembly of PML NBs is the consequence of the disappearance of PML/RARalpha. Tretinoin 76-78 PML nuclear body scaffold Homo sapiens 28-31 9657734-2 1998 ATRA probably induces differentiation of acute promyelocytic leukemia (APL) cells by binding to the E-domain of the RARalpha portion (RARalpha /E-domain) of PML/RARalpha chimeric protein. Tretinoin 0-4 PML nuclear body scaffold Homo sapiens 157-160 9694705-0 1998 Leukemic cellular retinoic acid resistance and missense mutations in the PML-RARalpha fusion gene after relapse of acute promyelocytic leukemia from treatment with all-trans retinoic acid and intensive chemotherapy. Tretinoin 174-187 PML nuclear body scaffold Homo sapiens 73-76 9694705-1 1998 This study evaluated whether relapse of acute promyelocytic leukemia (APL) patients from clinical remissions achieved and/or maintained with all-trans retinoic acid (RA) in combination with intensive chemotherapy is associated with leukemic cellular resistance to RA and with alterations in the PML-RARalpha fusion gene. Tretinoin 166-168 PML nuclear body scaffold Homo sapiens 295-298 9694705-10 1998 We conclude that APL cellular resistance occurs with high incidence after relapse from RA + DA therapy administered in a nonconcurrent manner and that mutations in the RARalpha region of the PML-RARalpha gene are present in and likely mechanistically involved in RA resistance in a subset of these cases. Tretinoin 87-89 PML nuclear body scaffold Homo sapiens 191-194 9657734-10 1998 These findings suggest that mutations in the RARalpha /E-domain of the PML/RARalpha chimeric gene may confer clinical resistance to ATRA therapy in patients with APL. Tretinoin 132-136 PML nuclear body scaffold Homo sapiens 71-74 9671405-8 1998 The addition of retinoic acid abrogated the PMLRARalpha, but not PML-induced stimulation of GAL4/Fos activity in a dose-dependent manner. Tretinoin 16-29 PML nuclear body scaffold Homo sapiens 44-47 9624536-6 1998 The two cases expressing PML/RARA presented with an immunostaining pattern typical of APL and a positive response to ATRA, whereas the APL case expressing only a RARA/PML fusion transcript exhibited an immunostaining pattern typical of non-APL cells, and was resistant to ATRA. Tretinoin 117-121 PML nuclear body scaffold Homo sapiens 25-28 9624536-7 1998 Our results confirm that sensitivity to ATRA requires expression of PML/RARA and strongly correlates with immunostaining, and demonstrate that expression of RARA/PML alone is sufficient for a cytological APL phenotype, but does not confer sensitivity to ATRA. Tretinoin 40-44 PML nuclear body scaffold Homo sapiens 68-71 9596679-5 1998 Thus, As2O3- or retinoic acid (RA)-induced PML/RARalpha degradation may be a prerequisite, but is not sufficient for the full differentiative/apoptotic response to these drugs. Tretinoin 16-29 PML nuclear body scaffold Homo sapiens 43-46 9558392-0 1998 Constitutive expression of the promyelocytic leukemia-associated oncogene PML-RARalpha in TF1 cells: isoform-specific and retinoic acid-dependent effects on growth, bcl-2 expression, and apoptosis. Tretinoin 122-135 PML nuclear body scaffold Homo sapiens 74-77 9596679-5 1998 Thus, As2O3- or retinoic acid (RA)-induced PML/RARalpha degradation may be a prerequisite, but is not sufficient for the full differentiative/apoptotic response to these drugs. Tretinoin 31-33 PML nuclear body scaffold Homo sapiens 43-46 9558392-5 1998 Treatment with all-trans retinoic acid (ATRA) inhibited cell growth and caused apoptosis only in PML-RARalpha-expressing cells, and these effects of ATRA were more marked in cells expressing the L isoform. Tretinoin 15-38 PML nuclear body scaffold Homo sapiens 97-100 9558392-5 1998 Treatment with all-trans retinoic acid (ATRA) inhibited cell growth and caused apoptosis only in PML-RARalpha-expressing cells, and these effects of ATRA were more marked in cells expressing the L isoform. Tretinoin 40-44 PML nuclear body scaffold Homo sapiens 97-100 9558392-6 1998 ATRA treatment also led to downregulation of bcl-2 and endogenous RARalpha in PML-RARalpha-expressing cells, but had little effect on the level of exogenously expressed PML-RARalpha. Tretinoin 0-4 PML nuclear body scaffold Homo sapiens 78-81 9558392-7 1998 We conclude that (1) subtle differences exist in the biologic activities of the L and S isoforms of PML-RARalpha, and (2) both isoforms are capable of transducing an ATRA-mediated signal that leads to downregulation of bcl-2 and induction of programmed cell death. Tretinoin 166-170 PML nuclear body scaffold Homo sapiens 100-103 9369431-0 1997 Mutant AF-2 domain of PML-RARalpha in retinoic acid-resistant NB4 cells: differentiation induced by RA is triggered directly through PML-RARalpha and its down-regulation in acute promyelocytic leukemia. Tretinoin 38-51 PML nuclear body scaffold Homo sapiens 22-25 9486654-3 1998 PML-RARalpha APL patients achieve complete remission following treatments with pharmacological doses of retinoic acids (RA); in contrast, PLZF-RARalpha patients respond very poorly, if at all. Tretinoin 104-118 PML nuclear body scaffold Homo sapiens 0-3 9486654-3 1998 PML-RARalpha APL patients achieve complete remission following treatments with pharmacological doses of retinoic acids (RA); in contrast, PLZF-RARalpha patients respond very poorly, if at all. Tretinoin 4-6 PML nuclear body scaffold Homo sapiens 0-3 9486655-4 1998 However, treatment with RA induces differentiation of leukaemic blast cells and disease remission in PML-RARalpha APLs, whereas PLZF-RARa APLs are resistant to RA. Tretinoin 24-26 PML nuclear body scaffold Homo sapiens 101-104 9486655-4 1998 However, treatment with RA induces differentiation of leukaemic blast cells and disease remission in PML-RARalpha APLs, whereas PLZF-RARa APLs are resistant to RA. Tretinoin 105-107 PML nuclear body scaffold Homo sapiens 101-104 9486655-8 1998 High doses of RA release histone deacetylase activity from PML-RARalpha, but not from PLZF-RARalpha. Tretinoin 14-16 PML nuclear body scaffold Homo sapiens 59-62 9486655-10 1998 Therefore, recruitment of histone deacetylase is crucial to the transforming potential of APL fusion proteins, and the different effects of RA on the stability of the PML-RARalpha and PLZF-RARalpha co-repressor complexes determines the differential response of APLs to RA. Tretinoin 140-142 PML nuclear body scaffold Homo sapiens 167-170 9486655-10 1998 Therefore, recruitment of histone deacetylase is crucial to the transforming potential of APL fusion proteins, and the different effects of RA on the stability of the PML-RARalpha and PLZF-RARalpha co-repressor complexes determines the differential response of APLs to RA. Tretinoin 171-173 PML nuclear body scaffold Homo sapiens 167-170 9460497-1 1998 A woman with t(15;17) and PML/RAR alpha positive acute promyelocytic leukemia (APL-M3v) achieved a complete remission (CR) with cytogenetic and molecular conversion, after one-month ATRA plus idarubicin treatment. Tretinoin 182-186 PML nuclear body scaffold Homo sapiens 26-39 9535176-2 1997 The PML-RAR alpha fusion gene plays an important role in leukemogenesis through antagonizing retinoic acid signalling and the regulatory pathways mediated by PML. Tretinoin 93-106 PML nuclear body scaffold Homo sapiens 4-7 9535176-4 1997 The therapeutic effect of ATRA in APL has been associated with the direct modulation of PML-RAR alpha, the restoration of the differentiation pathways regulated by wild-type RAR/retinoid X receptor heterodimer and PML. Tretinoin 26-30 PML nuclear body scaffold Homo sapiens 88-91 9535176-4 1997 The therapeutic effect of ATRA in APL has been associated with the direct modulation of PML-RAR alpha, the restoration of the differentiation pathways regulated by wild-type RAR/retinoid X receptor heterodimer and PML. Tretinoin 26-30 PML nuclear body scaffold Homo sapiens 178-217 9531570-0 1998 Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia. Tretinoin 8-21 PML nuclear body scaffold Homo sapiens 79-83 9531570-1 1998 Typical acute promyelocytic leukemia (APL) is associated with expression of the PML-RARalpha fusion protein and responsiveness to treatment with all-trans retinoic acid (ATRA). Tretinoin 145-168 PML nuclear body scaffold Homo sapiens 80-84 9531570-1 1998 Typical acute promyelocytic leukemia (APL) is associated with expression of the PML-RARalpha fusion protein and responsiveness to treatment with all-trans retinoic acid (ATRA). Tretinoin 170-174 PML nuclear body scaffold Homo sapiens 80-84 9531570-5 1998 Although pharmacologic concentration of ATRA could still induce dissociation of N-CoR from PML-RARalpha, it had a very little effect on its association with the PLZF-RARalpha fusion protein. Tretinoin 40-44 PML nuclear body scaffold Homo sapiens 91-95 9531570-8 1998 As the above-noted results predict, histone deacetylase inhibitors antagonize oncogenic activities of the PML-RARalpha fusion protein and partially relieve transcriptional repression by PLZF as well as inhibitory effect of PLZF-RARalpha on ATRA response. Tretinoin 240-244 PML nuclear body scaffold Homo sapiens 106-110 9369431-0 1997 Mutant AF-2 domain of PML-RARalpha in retinoic acid-resistant NB4 cells: differentiation induced by RA is triggered directly through PML-RARalpha and its down-regulation in acute promyelocytic leukemia. Tretinoin 38-51 PML nuclear body scaffold Homo sapiens 133-136 9369431-0 1997 Mutant AF-2 domain of PML-RARalpha in retinoic acid-resistant NB4 cells: differentiation induced by RA is triggered directly through PML-RARalpha and its down-regulation in acute promyelocytic leukemia. Tretinoin 26-28 PML nuclear body scaffold Homo sapiens 22-25 9369431-0 1997 Mutant AF-2 domain of PML-RARalpha in retinoic acid-resistant NB4 cells: differentiation induced by RA is triggered directly through PML-RARalpha and its down-regulation in acute promyelocytic leukemia. Tretinoin 26-28 PML nuclear body scaffold Homo sapiens 133-136 9369431-4 1997 Immunostaining of NB4/RA cells using anti-PML antibody showed a microgranular pattern which was not restored even by the combination of RA and 8-CPT-cAMP, whereas the microgranular pattern in NB4 cells was rapidly restored to the normal speckled pattern by RA. Tretinoin 22-24 PML nuclear body scaffold Homo sapiens 42-45 9369431-4 1997 Immunostaining of NB4/RA cells using anti-PML antibody showed a microgranular pattern which was not restored even by the combination of RA and 8-CPT-cAMP, whereas the microgranular pattern in NB4 cells was rapidly restored to the normal speckled pattern by RA. Tretinoin 136-138 PML nuclear body scaffold Homo sapiens 42-45 9369431-8 1997 These data suggest that differentiation of APL by RA is triggered directly through PML-RARalpha, and is associated with its degradation. Tretinoin 50-52 PML nuclear body scaffold Homo sapiens 83-86 9234742-2 1997 APLs with the PML-RAR alpha or the PLZF-RAR alpha fusion protein are phenotypically indistinguishable except that they differ in their sensitivity to retinoic acid (RA)-induced differentiation: PML-RAR alpha blasts are sensitive to RA and patients enter disease remission after RA treatment, while patients with PLZF-RAR alpha do not. Tretinoin 150-163 PML nuclear body scaffold Homo sapiens 14-17 9242550-3 1997 T-RA is an effective inducer of clinical remission only in patients carrying the t(15;17) and expressing the PML/RAR alpha products. Tretinoin 0-4 PML nuclear body scaffold Homo sapiens 109-122 9242550-9 1997 Moreover, two different high-affinity 9-cis-RA binding sites (Kd = 0.45 and 0.075 nmol/L) were detectable in the bcr3-PML/RAR alpha product but not in the bcr1-PML/RAR alpha product (Kd = 0.77 nmol/L). Tretinoin 38-46 PML nuclear body scaffold Homo sapiens 118-121 9242550-9 1997 Moreover, two different high-affinity 9-cis-RA binding sites (Kd = 0.45 and 0.075 nmol/L) were detectable in the bcr3-PML/RAR alpha product but not in the bcr1-PML/RAR alpha product (Kd = 0.77 nmol/L). Tretinoin 38-46 PML nuclear body scaffold Homo sapiens 160-163 9242550-10 1997 By competition binding experiments we showed that 9-cis-RA binds with higher specificity to the bcr3-PML/RAR alpha isoform than to the bcr1-PML/RAR alpha or RAR alpha. Tretinoin 50-58 PML nuclear body scaffold Homo sapiens 101-104 9234742-2 1997 APLs with the PML-RAR alpha or the PLZF-RAR alpha fusion protein are phenotypically indistinguishable except that they differ in their sensitivity to retinoic acid (RA)-induced differentiation: PML-RAR alpha blasts are sensitive to RA and patients enter disease remission after RA treatment, while patients with PLZF-RAR alpha do not. Tretinoin 40-42 PML nuclear body scaffold Homo sapiens 194-197 9234742-4 1997 These data demonstrate that PML-RAR alpha and PLZF-RAR alpha have similar (inhibitory) effects on RA-independent differentiation and opposite (stimulatory or inhibitory) effects on RA-dependent differentiation and that they behave in vivo as RA-dependent enhancers or inhibitors of RA-responsive genes, respectively. Tretinoin 32-34 PML nuclear body scaffold Homo sapiens 28-31 9234742-5 1997 Their different activities on the RA signalling pathway might underlie the different responses of PML-RAR alpha and PLZF-RAR alpha APLs to RA treatment. Tretinoin 34-36 PML nuclear body scaffold Homo sapiens 98-101 9234742-5 1997 Their different activities on the RA signalling pathway might underlie the different responses of PML-RAR alpha and PLZF-RAR alpha APLs to RA treatment. Tretinoin 102-104 PML nuclear body scaffold Homo sapiens 98-101 9234742-2 1997 APLs with the PML-RAR alpha or the PLZF-RAR alpha fusion protein are phenotypically indistinguishable except that they differ in their sensitivity to retinoic acid (RA)-induced differentiation: PML-RAR alpha blasts are sensitive to RA and patients enter disease remission after RA treatment, while patients with PLZF-RAR alpha do not. Tretinoin 150-163 PML nuclear body scaffold Homo sapiens 194-197 9234742-2 1997 APLs with the PML-RAR alpha or the PLZF-RAR alpha fusion protein are phenotypically indistinguishable except that they differ in their sensitivity to retinoic acid (RA)-induced differentiation: PML-RAR alpha blasts are sensitive to RA and patients enter disease remission after RA treatment, while patients with PLZF-RAR alpha do not. Tretinoin 18-20 PML nuclear body scaffold Homo sapiens 14-17 9234742-2 1997 APLs with the PML-RAR alpha or the PLZF-RAR alpha fusion protein are phenotypically indistinguishable except that they differ in their sensitivity to retinoic acid (RA)-induced differentiation: PML-RAR alpha blasts are sensitive to RA and patients enter disease remission after RA treatment, while patients with PLZF-RAR alpha do not. Tretinoin 18-20 PML nuclear body scaffold Homo sapiens 194-197 9234742-2 1997 APLs with the PML-RAR alpha or the PLZF-RAR alpha fusion protein are phenotypically indistinguishable except that they differ in their sensitivity to retinoic acid (RA)-induced differentiation: PML-RAR alpha blasts are sensitive to RA and patients enter disease remission after RA treatment, while patients with PLZF-RAR alpha do not. Tretinoin 40-42 PML nuclear body scaffold Homo sapiens 194-197 15624327-7 1997 The differences between PML-RARalpha and PLZF-RARalpha may in part explain the apparent resistance of APL with t(11;17) to differentiating effect of all-trans retinoic acid (ATRA). Tretinoin 159-172 PML nuclear body scaffold Homo sapiens 24-27 15625843-1 1997 OBJECTIVE: To analyze the conversion of RARalpha/PML gene in acute promyelocytic leukemia (APL) patients before and after treatment with all-trans retinoic acid (ATRA) followed by intensive consolidation chemotherapy (ICC) and allogeneic bone marrow transplantation (allo-BMT). Tretinoin 137-160 PML nuclear body scaffold Homo sapiens 49-52 15625843-1 1997 OBJECTIVE: To analyze the conversion of RARalpha/PML gene in acute promyelocytic leukemia (APL) patients before and after treatment with all-trans retinoic acid (ATRA) followed by intensive consolidation chemotherapy (ICC) and allogeneic bone marrow transplantation (allo-BMT). Tretinoin 162-166 PML nuclear body scaffold Homo sapiens 49-52 15625843-3 1997 RESULTS: RARalpha/PML fusion gene was positive in 75% of the patients after achieving complete remission with ATRA, and turned negative in 83% of the patients after ICC. Tretinoin 110-114 PML nuclear body scaffold Homo sapiens 18-21 15624327-7 1997 The differences between PML-RARalpha and PLZF-RARalpha may in part explain the apparent resistance of APL with t(11;17) to differentiating effect of all-trans retinoic acid (ATRA). Tretinoin 174-178 PML nuclear body scaffold Homo sapiens 24-27 9089745-1 1997 We describe here the first case of childhood acute promyelocytic leukemia (APL) with cutaneous infiltration of leukemic cells following treatment with all-trans retinoic acid (ATRA) confirmed by immunostaining and polymerase chain reaction for PML/RAR alpha. Tretinoin 151-174 PML nuclear body scaffold Homo sapiens 244-257 9108090-1 1997 Acute promyelocytic leukemia (APL) is associated with the t(15;17) translocation, which generates a PML/RAR alpha fusion protein between PML, a growth suppressor localized on nuclear matrix-associated bodies, and RAR alpha, a nuclear receptor for retinoic acid (RA). Tretinoin 247-260 PML nuclear body scaffold Homo sapiens 100-113 9108090-1 1997 Acute promyelocytic leukemia (APL) is associated with the t(15;17) translocation, which generates a PML/RAR alpha fusion protein between PML, a growth suppressor localized on nuclear matrix-associated bodies, and RAR alpha, a nuclear receptor for retinoic acid (RA). Tretinoin 247-260 PML nuclear body scaffold Homo sapiens 100-103 9108090-1 1997 Acute promyelocytic leukemia (APL) is associated with the t(15;17) translocation, which generates a PML/RAR alpha fusion protein between PML, a growth suppressor localized on nuclear matrix-associated bodies, and RAR alpha, a nuclear receptor for retinoic acid (RA). Tretinoin 104-106 PML nuclear body scaffold Homo sapiens 100-103 9108090-8 1997 Thus, RA and arsenic target RAR alpha and PML, respectively, but both induce the degradation of the PML/RAR alpha fusion protein, which should contribute to their therapeutic effects. Tretinoin 6-8 PML nuclear body scaffold Homo sapiens 42-45 9089745-1 1997 We describe here the first case of childhood acute promyelocytic leukemia (APL) with cutaneous infiltration of leukemic cells following treatment with all-trans retinoic acid (ATRA) confirmed by immunostaining and polymerase chain reaction for PML/RAR alpha. Tretinoin 176-180 PML nuclear body scaffold Homo sapiens 244-257 8874178-3 1996 We now show that the PML/RAR alpha fusion product is directly downregulated in response to retinoic acid (tRA) treatment in the human APL cell line, NB4. Tretinoin 91-104 PML nuclear body scaffold Homo sapiens 21-34 8916959-5 1996 Similarly, interferons could act on APL cells, alone or in combination with all-trans retinoic acid (RA), especially if the PML/RAR alpha fusion transcript that results from the t(15; 17) is induced by interferon. Tretinoin 86-99 PML nuclear body scaffold Homo sapiens 124-137 8916959-5 1996 Similarly, interferons could act on APL cells, alone or in combination with all-trans retinoic acid (RA), especially if the PML/RAR alpha fusion transcript that results from the t(15; 17) is induced by interferon. Tretinoin 101-103 PML nuclear body scaffold Homo sapiens 124-137 8956873-4 1996 The unusual PML-RARA fusion may be related to this patient"s poor response to induction therapy with all-trans-retinoic acid. Tretinoin 101-124 PML nuclear body scaffold Homo sapiens 12-15 8986606-0 1996 The PML and PML/RARalpha domains: from autoimmunity to molecular oncology and from retinoic acid to arsenic. Tretinoin 83-96 PML nuclear body scaffold Homo sapiens 4-7 8986606-0 1996 The PML and PML/RARalpha domains: from autoimmunity to molecular oncology and from retinoic acid to arsenic. Tretinoin 83-96 PML nuclear body scaffold Homo sapiens 12-15 8986606-5 1996 In APL, the PML/RARalpha fusion interferes with both the retinoic acid (RA) response and PML localization on nuclear bodies, but the respective contribution of each defect to leukemogenesis is unclear. Tretinoin 57-70 PML nuclear body scaffold Homo sapiens 12-15 8986606-5 1996 In APL, the PML/RARalpha fusion interferes with both the retinoic acid (RA) response and PML localization on nuclear bodies, but the respective contribution of each defect to leukemogenesis is unclear. Tretinoin 16-18 PML nuclear body scaffold Homo sapiens 12-15 8986606-5 1996 In APL, the PML/RARalpha fusion interferes with both the retinoic acid (RA) response and PML localization on nuclear bodies, but the respective contribution of each defect to leukemogenesis is unclear. Tretinoin 16-18 PML nuclear body scaffold Homo sapiens 89-92 8806687-9 1996 However, following all trans retinoic acid treatment of NB4 cells a significant relocalisation of PIC1 and PML is observed. Tretinoin 29-42 PML nuclear body scaffold Homo sapiens 107-110 8826895-2 1996 Treatment with all-trans-retinoic-acid (ATRA) resulted in rapid normalization of the coagulopathy and complete remission of PML within 2 weeks. Tretinoin 15-38 PML nuclear body scaffold Homo sapiens 124-127 8826895-2 1996 Treatment with all-trans-retinoic-acid (ATRA) resulted in rapid normalization of the coagulopathy and complete remission of PML within 2 weeks. Tretinoin 40-44 PML nuclear body scaffold Homo sapiens 124-127 8826895-4 1996 ATRA therapy for PML during late pregnancy was effective in reversing the maternal bleeding tendency and inducing a complete remission of the PML without evidence of teratogenicity. Tretinoin 0-4 PML nuclear body scaffold Homo sapiens 17-20 8790159-13 1996 However, although PML immunofluorescence staining is suitable for rapid determination of patients likely to benefit from ATRA, this approach does not obviate the need for cytogenetic and RT-PCR analysis of all patients entered into APL clinical trials, because both techniques provide additional information which may prove to be of independent prognostic significance. Tretinoin 121-125 PML nuclear body scaffold Homo sapiens 18-21 8703836-1 1996 The interaction of an exogenous PML/RAR alpha fusion gene associated with acute promyelocytic leukaemia, with all-trans retinoic acid (ATRA) was examined in two lymphoid cell lines. Tretinoin 110-133 PML nuclear body scaffold Homo sapiens 32-45 8703836-1 1996 The interaction of an exogenous PML/RAR alpha fusion gene associated with acute promyelocytic leukaemia, with all-trans retinoic acid (ATRA) was examined in two lymphoid cell lines. Tretinoin 135-139 PML nuclear body scaffold Homo sapiens 32-45 8703836-5 1996 The exogenous PML/RAR alpha fusion gene therefore probably mediates the effects of ATRA on cell growth and apoptosis in these cell lines. Tretinoin 83-87 PML nuclear body scaffold Homo sapiens 14-27 8810554-1 1996 We studied the quantitative changes in PML/retinoic acid receptor alpha (PML/RAR alpha) fusion mRNA using the reverse transcriptase-polymerase chain reaction (RT-PCR) and the in vitro differentiation of leukemic cells from eight acute promyelocytic leukemia (APL) patients during treatment with all-trans retinoic acid (ATRA). Tretinoin 43-56 PML nuclear body scaffold Homo sapiens 73-86 8810554-2 1996 In three patients, the intensity of the chimeric PML/RAR alpha bands decreased rapidly after the start of ATRA therapy. Tretinoin 106-110 PML nuclear body scaffold Homo sapiens 49-62 8684004-2 1996 Detection of the PML/RARalpha fusion gene in APL blasts is critical to start promptly the specific therapy with all-trans retinoic acid (ATRA). Tretinoin 112-135 PML nuclear body scaffold Homo sapiens 17-20 8684004-2 1996 Detection of the PML/RARalpha fusion gene in APL blasts is critical to start promptly the specific therapy with all-trans retinoic acid (ATRA). Tretinoin 137-141 PML nuclear body scaffold Homo sapiens 17-20 8819070-2 1996 The t(15;17) leads to the formation of two reciprocal fusion genes, PML/RARA on chromosome 15 and RARA/PML on chromosome 17; it is responsible for the unique response of the disease to retinoic acid (ATRA) treatment. Tretinoin 185-198 PML nuclear body scaffold Homo sapiens 68-71 8819070-2 1996 The t(15;17) leads to the formation of two reciprocal fusion genes, PML/RARA on chromosome 15 and RARA/PML on chromosome 17; it is responsible for the unique response of the disease to retinoic acid (ATRA) treatment. Tretinoin 185-198 PML nuclear body scaffold Homo sapiens 103-106 8819070-2 1996 The t(15;17) leads to the formation of two reciprocal fusion genes, PML/RARA on chromosome 15 and RARA/PML on chromosome 17; it is responsible for the unique response of the disease to retinoic acid (ATRA) treatment. Tretinoin 200-204 PML nuclear body scaffold Homo sapiens 68-71 8819070-2 1996 The t(15;17) leads to the formation of two reciprocal fusion genes, PML/RARA on chromosome 15 and RARA/PML on chromosome 17; it is responsible for the unique response of the disease to retinoic acid (ATRA) treatment. Tretinoin 200-204 PML nuclear body scaffold Homo sapiens 103-106 8649786-0 1996 Differential changes of retinoid-X-receptor (RXR alpha) and its RAR alpha and PML-RAR alpha partners induced by retinoic acid and cAMP distinguish maturation sensitive and resistant t(15;17) promyelocytic leukemia NB4 cells. Tretinoin 112-125 PML nuclear body scaffold Homo sapiens 78-81 8826895-4 1996 ATRA therapy for PML during late pregnancy was effective in reversing the maternal bleeding tendency and inducing a complete remission of the PML without evidence of teratogenicity. Tretinoin 0-4 PML nuclear body scaffold Homo sapiens 142-145 8881287-5 1996 The fusion protein PML-RAR, which is not localized in nuclear bodies, also enhanced the transactivating activity of PR but this effect was totally suppressed by the administration of retinoic acid. Tretinoin 183-196 PML nuclear body scaffold Homo sapiens 19-22 8634442-2 1996 In the present study, we show that t-RA treatment dramatically induced type II transglutaminase (type II TGase) expression in cells carrying the t(15;17) translocation and expressing the PML-RARalpha product such as the APL-derived NB4 cell line and fresh leukemic cells from APL patients. Tretinoin 35-39 PML nuclear body scaffold Homo sapiens 187-190 8721678-7 1996 Current data suggest that PML-RAR alpha and PLZF-RAR alpha fusion receptors may play an important role in the development of APL and that PML-RAR alpha could be the target of ATRA differentiation therapy. Tretinoin 175-179 PML nuclear body scaffold Homo sapiens 138-141 8622986-4 1996 PLZF-RARalpha and PML-RARalpha have essentially the same ligand-binding affinities and can bind in vitro to retinoic acid response elements (RAREs) as homodimers or heterodimers with RXRalpha. Tretinoin 108-121 PML nuclear body scaffold Homo sapiens 18-21 8622986-8 1996 These different protein-protein interactions and the target gene specificities of PLZF-RARalpha and PML-RARalpha may underlie, at least in part, the apparent resistance of APL with t(11;17) to differentiation effects of all-trans-retinoic acid. Tretinoin 224-243 PML nuclear body scaffold Homo sapiens 100-103 7934155-4 1994 Its cellular distribution is completely reorganized when compared to that of PML: the hybrid is found in multiple small nuclear substructures and upon retinoic acid treatment, it goes back to the normal PML localization, that is in typical well organized nuclear bodies. Tretinoin 151-164 PML nuclear body scaffold Homo sapiens 77-80 7672716-3 1995 In four of the patients PCR was positive for the PML/RAR alpha transcript immediately after ATRA treatment and/or after the first consolidation chemotherapy course. Tretinoin 92-96 PML nuclear body scaffold Homo sapiens 49-62 8773125-2 1995 The presence of PML/RAR-alpha fusion gene produced as a result of the unique chromosomal translocation in APML is a marker of the sensitivity to ATRA therapy. Tretinoin 145-149 PML nuclear body scaffold Homo sapiens 16-19 7697468-9 1994 Recently it has been shown that PML/RAR alpha can be modulated directly by ATRA. Tretinoin 75-79 PML nuclear body scaffold Homo sapiens 32-45 8605120-11 1995 Whereas RARA rearrangement appears sufficient for an APL-like phenotype, it seems that the presence of a classical PML/RARA is required for typical APL with response to ATRA. Tretinoin 169-173 PML nuclear body scaffold Homo sapiens 115-118 7658715-0 1995 Isoforms of PML-retinoic acid receptor alpha fused transcripts affect neither clinical features of acute promyelocytic leukemia nor prognosis after treatment with all-trans retinoic acid. Tretinoin 16-29 PML nuclear body scaffold Homo sapiens 12-15 7620182-7 1995 Reorganization of the PML labeling into PODs with normal appearance was observed in cells from patients who received RA. Tretinoin 117-119 PML nuclear body scaffold Homo sapiens 22-25 7784078-3 1995 Clinical remissions induced by all-trans-retinoic acid (RA) treatment of APL patients are linked to expression of PML/RAR apha, a transcription factor with reported dominant negative functions. Tretinoin 31-54 PML nuclear body scaffold Homo sapiens 114-117 7784078-3 1995 Clinical remissions induced by all-trans-retinoic acid (RA) treatment of APL patients are linked to expression of PML/RAR apha, a transcription factor with reported dominant negative functions. Tretinoin 56-58 PML nuclear body scaffold Homo sapiens 114-117 7869768-0 1995 Effect of retinoic acid isomers on proliferation, differentiation and PML relocalization in the APL cell line NB4. Tretinoin 10-23 PML nuclear body scaffold Homo sapiens 70-73 7845010-10 1995 Disappearance of the PML/RAR alpha rearrangement after ATRA suggests that ATRA is effective against minimal residual disease. Tretinoin 55-59 PML nuclear body scaffold Homo sapiens 21-34 7845010-10 1995 Disappearance of the PML/RAR alpha rearrangement after ATRA suggests that ATRA is effective against minimal residual disease. Tretinoin 74-78 PML nuclear body scaffold Homo sapiens 21-34 7719245-13 1995 The comparison of the biological activities mediated by PML-RAR alpha and PLZF-RAR alpha may give new insights into the pathogenesis as well as the mechanisms of ATRA-induced differentiation in APL. Tretinoin 162-166 PML nuclear body scaffold Homo sapiens 56-59 7831584-4 1994 The presence of the PML/retinoic acid receptor-alpha (PML/RAR-alpha) fusion gene, produced as a result of the unique chromosomal translocation in APL, is a marker of sensitivity to ATRA. Tretinoin 181-185 PML nuclear body scaffold Homo sapiens 20-23 7831584-4 1994 The presence of the PML/retinoic acid receptor-alpha (PML/RAR-alpha) fusion gene, produced as a result of the unique chromosomal translocation in APL, is a marker of sensitivity to ATRA. Tretinoin 181-185 PML nuclear body scaffold Homo sapiens 54-67 7519122-0 1994 PML/RAR alpha+ U937 mutant and NB4 cell lines: retinoic acid restores the monocytic differentiation response to vitamin D3. Tretinoin 47-60 PML nuclear body scaffold Homo sapiens 0-13 7754440-1 1994 PURPOSE: To assess the results attained with all-trans-retinoic acid (ATRA) in a group of Cuban patients with acute promyelocytic leukaemia (PML). Tretinoin 45-68 PML nuclear body scaffold Homo sapiens 141-144 7754440-1 1994 PURPOSE: To assess the results attained with all-trans-retinoic acid (ATRA) in a group of Cuban patients with acute promyelocytic leukaemia (PML). Tretinoin 70-74 PML nuclear body scaffold Homo sapiens 141-144 7754440-20 1994 The efficacy of ATRA, in general terms, in the induction of CR in PML seems confirmed by these results. Tretinoin 16-20 PML nuclear body scaffold Homo sapiens 66-69 7934155-4 1994 Its cellular distribution is completely reorganized when compared to that of PML: the hybrid is found in multiple small nuclear substructures and upon retinoic acid treatment, it goes back to the normal PML localization, that is in typical well organized nuclear bodies. Tretinoin 151-164 PML nuclear body scaffold Homo sapiens 203-206 7934155-6 1994 Expression of PML-RAR alpha in HL60 or U937 cell has been shown to block their maturation while it can force their differentiation at high doses of retinoic acid. Tretinoin 148-161 PML nuclear body scaffold Homo sapiens 14-17 7934155-7 1994 Different mechanisms are proposed to explain how PML-RAR alpha blocks differentiation and how this may be reversed by retinoic acid. Tretinoin 118-131 PML nuclear body scaffold Homo sapiens 49-52 8144129-2 1994 We examined bone marrow cells by reverse transcriptase-polymerase chain reaction (RT-PCR) to detect residual PML/RAR alpha mRNA-containing cells following treatment with all-trans retinoic acid (ATRA) and cytotoxic chemotherapy in a patient with APL. Tretinoin 180-193 PML nuclear body scaffold Homo sapiens 109-122 8152308-6 1994 We expressed the PML/RAR alpha protein in U937 myeloid precursor cell line and show that they: 1) lose the capacity to differentiate under the action of different stimuli (vitamin D3, transforming growth factor beta 1); ii) acquire enhanced sensitivity to retinoic acid; iii) exhibit a higher growth rate that is due to a reduction in apoptotic cell death. Tretinoin 256-269 PML nuclear body scaffold Homo sapiens 17-30 8144129-2 1994 We examined bone marrow cells by reverse transcriptase-polymerase chain reaction (RT-PCR) to detect residual PML/RAR alpha mRNA-containing cells following treatment with all-trans retinoic acid (ATRA) and cytotoxic chemotherapy in a patient with APL. Tretinoin 195-199 PML nuclear body scaffold Homo sapiens 109-122 8144129-4 1994 We show that PML/RAR alpha mRNA was still detectable despite clinical remission following ATRA treatment, but undetectable following consolidation with chemotherapy. Tretinoin 90-94 PML nuclear body scaffold Homo sapiens 13-26 8293468-0 1994 Retinoic acid regulates aberrant nuclear localization of PML-RAR alpha in acute promyelocytic leukemia cells. Tretinoin 0-13 PML nuclear body scaffold Homo sapiens 57-60 8290265-0 1994 The PML-RAR alpha gene product of the t(15;17) translocation inhibits retinoic acid-induced granulocytic differentiation and mediated transactivation in human myeloid cells. Tretinoin 70-83 PML nuclear body scaffold Homo sapiens 4-7 8290265-3 1994 In non hematopoietic cells, the transfected PML-RAR alpha product binds all trans retinoic acid and exhibits altered transactivating properties when compared with RAR alpha. Tretinoin 82-95 PML nuclear body scaffold Homo sapiens 44-47 8290265-5 1994 We find that in myeloid cell lines responsive to retinoic acid, PML-RAR alpha blocks retinoic acid mediated transactivation and totally abrogates the retinoic acid mediated granulocytic differentiation. Tretinoin 49-62 PML nuclear body scaffold Homo sapiens 64-67 8290265-5 1994 We find that in myeloid cell lines responsive to retinoic acid, PML-RAR alpha blocks retinoic acid mediated transactivation and totally abrogates the retinoic acid mediated granulocytic differentiation. Tretinoin 85-98 PML nuclear body scaffold Homo sapiens 64-67 8290265-5 1994 We find that in myeloid cell lines responsive to retinoic acid, PML-RAR alpha blocks retinoic acid mediated transactivation and totally abrogates the retinoic acid mediated granulocytic differentiation. Tretinoin 85-98 PML nuclear body scaffold Homo sapiens 64-67 8290265-7 1994 The fact that high doses of all-trans retinoic acid relieve the inhibitory effect of PML-RAR alpha corroborates the therapeutic effect of all-trans retinoic acid in APL patients. Tretinoin 32-51 PML nuclear body scaffold Homo sapiens 85-88 8415704-1 1993 We report here that the fusion of PML, a nuclear protein defined by the t(15;17) chromosomal translocation in acute promyelocytic leukemia, with retinoic acid receptor alpha (RAR alpha) changes the RAR alpha from a retinoic acid (RA)-dependent inhibitor to a RA-dependent activator of AP-1 transcriptional activity. Tretinoin 145-158 PML nuclear body scaffold Homo sapiens 34-37 8415704-1 1993 We report here that the fusion of PML, a nuclear protein defined by the t(15;17) chromosomal translocation in acute promyelocytic leukemia, with retinoic acid receptor alpha (RAR alpha) changes the RAR alpha from a retinoic acid (RA)-dependent inhibitor to a RA-dependent activator of AP-1 transcriptional activity. Tretinoin 175-177 PML nuclear body scaffold Homo sapiens 34-37 8415704-1 1993 We report here that the fusion of PML, a nuclear protein defined by the t(15;17) chromosomal translocation in acute promyelocytic leukemia, with retinoic acid receptor alpha (RAR alpha) changes the RAR alpha from a retinoic acid (RA)-dependent inhibitor to a RA-dependent activator of AP-1 transcriptional activity. Tretinoin 198-200 PML nuclear body scaffold Homo sapiens 34-37 8415704-6 1993 In view of the association between AP-1 activity and hemopoietic differentiation, we suggest that these properties of PML-RAR alpha could contribute to the leukemic phenotype and its response to RA. Tretinoin 122-124 PML nuclear body scaffold Homo sapiens 118-121 8394219-5 1993 We expressed the PML-RAR alpha protein in U937 myeloid precursor cells and showed that they lost the capacity to differentiate under the action of different stimuli (vitamin D3 and transforming growth factor beta 1), acquired enhanced sensitivity to retinoic acid, and exhibited a higher growth rate consequent to diminished apoptotic cell death. Tretinoin 250-263 PML nuclear body scaffold Homo sapiens 17-20 8400236-6 1993 RA treatment of NB4 cells or clones expressing PML/RAR alpha gradually leads to a PML pattern before apparent morphologic maturation. Tretinoin 0-2 PML nuclear body scaffold Homo sapiens 47-60 8400236-6 1993 RA treatment of NB4 cells or clones expressing PML/RAR alpha gradually leads to a PML pattern before apparent morphologic maturation. Tretinoin 0-2 PML nuclear body scaffold Homo sapiens 47-50 8400236-8 1993 Strikingly, in 4 patients, after 1 to 2 weeks of RA therapy, the speckled nuclear PML pattern reappeared concomitant with the onset of differentiation. Tretinoin 49-51 PML nuclear body scaffold Homo sapiens 82-85 8400236-9 1993 These results establish that fusion of PML to RAR alpha results in an altered localization of PML that is reverted upon RA treatment. Tretinoin 46-48 PML nuclear body scaffold Homo sapiens 39-42 8400236-9 1993 These results establish that fusion of PML to RAR alpha results in an altered localization of PML that is reverted upon RA treatment. Tretinoin 46-48 PML nuclear body scaffold Homo sapiens 94-97 34405393-7 2021 In conclusion, the present long-term follow-up study further confirmed the high cure probability of ATRA plus oral arsenic as front-line therapy for non-high-risk APL and showed that the PML-RARA transcript level at the end of induction therapy was associated with relapse. Tretinoin 100-104 PML nuclear body scaffold Homo sapiens 187-190 8396481-7 1993 Preliminary results suggest that the PML/RAR alpha fusion protein is responsible for two important properties of the APL phenotype: the differentiation block characteristic of the leukemic blasts and the high sensitivity of the blasts to the differentiative action of retinoic acid (RA) both in vivo and in vitro. Tretinoin 268-281 PML nuclear body scaffold Homo sapiens 37-50 8018944-8 1993 (5) It seems likely that the fusion gene PML-RARA plays an important role in APL leukemogenesis and in its response to the ATRA treatment. Tretinoin 123-127 PML nuclear body scaffold Homo sapiens 41-44 1339190-6 1992 The DNA-binding motifs of both the RARA and PML proteins, together with the ligand-binding domain of RARA, are combined in a single fusion protein which may dysregulate either retinoic acid or PML-sensitive pathways. Tretinoin 176-189 PML nuclear body scaffold Homo sapiens 44-47 1339190-9 1992 The PML-RARA chimaeric protein is presumably the target during the striking differentiation therapy achieved with all-trans retinoic acid. Tretinoin 124-137 PML nuclear body scaffold Homo sapiens 4-7 15894607-0 2005 Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Tretinoin 50-63 PML nuclear body scaffold Homo sapiens 123-145 34047175-0 2021 A Pin1/PML/P53 axis activated by retinoic acid in NPM-1c-acute myeloid leukemia. Tretinoin 33-46 PML nuclear body scaffold Homo sapiens 7-10 35622143-1 2022 Acute promyelocytic leukemia (APL) is a hematological malignancy driven by the oncoprotein PML-RARalpha, which can be treated with arsenic trioxide (As2O3) or/and all-trans retinoic acid. Tretinoin 166-186 PML nuclear body scaffold Homo sapiens 91-94 34047175-4 2021 Here, we demonstrate that PML is required to initiate RA-driven NPM-1c degradation, P53 activation and cell death. Tretinoin 54-56 PML nuclear body scaffold Homo sapiens 26-29 34047175-5 2021 Mechanistically, RA enhances PML basal expression through inhibition of activated Pin1, prior to NPM-1c degradation. Tretinoin 17-19 PML nuclear body scaffold Homo sapiens 29-32 33957999-2 2021 More than 95% of patients with this disease belong to typical APL, which express PML-RARA and are sensitive to differentiation induction therapy containing all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), and they exhibit an excellent clinical outcome. Tretinoin 181-185 PML nuclear body scaffold Homo sapiens 81-84 32854112-5 2021 All-trans retinoic acid and arsenic trioxide, two widely used drugs in APL therapy, exert synergistic effects on controlling super-enhancer-associated PML/RARalpha-regulated targets in APL cells. Tretinoin 0-23 PML nuclear body scaffold Homo sapiens 151-154 33901013-2 2021 Previous studies have primarily focused on the retinoic acid signaling pathway and how it is interfered with by promyelocytic leukemia/retinoic acid receptor-alpha (PML/RARalpha) fusion protein. Tretinoin 47-60 PML nuclear body scaffold Homo sapiens 165-168 33901013-6 2021 Consistently, mutation of the C/EBP sites or deletion of retinoic acid responsive elements (RAREs) and RARE half motifs abrogated the PML/RARalpha-mediated repression. Tretinoin 57-70 PML nuclear body scaffold Homo sapiens 134-137 32823855-5 2020 The first cancer showing ANXA8 upregulation was reported in acute promyelocytic leukemia (APL), which induces the differentiation arrest of promyelocytes due to defective RA signaling caused by RARA fusion genes as the PML-RARA gene. Tretinoin 171-173 PML nuclear body scaffold Homo sapiens 219-222 32036017-1 2020 The promyelocytic leukemia-retinoic acid receptor alpha (PML/RARalpha) is hypothesized to play a vital role in the pathogenesis of acute promyelocytic leukemia (APL). Tretinoin 27-40 PML nuclear body scaffold Homo sapiens 57-60 32380366-9 2020 Nevertheless, patients that required additional tests for diagnosis (PML immunofluorescence or molecular) started on ATRA later (28.5 versus 5.3 h; P < 0.0001), and had more thrombo-haemorrhagic complications (P = 0.04). Tretinoin 117-121 PML nuclear body scaffold Homo sapiens 69-72 32323584-2 2020 The cases of increased PML-RARa transcripts received induction treatment mainly based on ATRA and ATO. Tretinoin 89-93 PML nuclear body scaffold Homo sapiens 23-26 32274275-4 2020 With the initiation of all-trans retinoic acid, arsenic trioxide and gemtuzumab, the patient achieved remission, with absent PML/RARalpha by fluorescence in situ hybridization analysis. Tretinoin 23-46 PML nuclear body scaffold Homo sapiens 125-128