PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 26294332-0 2015 Evaluating frequency of PML-RARA mutations and conferring resistance to arsenic trioxide-based therapy in relapsed acute promyelocytic leukemia patients. Arsenic Trioxide 72-88 retinoic acid receptor alpha Homo sapiens 28-32 27030546-0 2016 PCGF2 negatively regulates arsenic trioxide-induced PML-RARA protein degradation via UBE2I inhibition in NB4 cells. Arsenic Trioxide 27-43 retinoic acid receptor alpha Homo sapiens 56-60 27030546-1 2016 Arsenic trioxide (ATO) is a therapeutic agent for acute promyelocytic leukemia (APL) which induces PML-RARA protein degradation via enhanced UBE2I-mediated sumoylation. Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 103-107 27030546-1 2016 Arsenic trioxide (ATO) is a therapeutic agent for acute promyelocytic leukemia (APL) which induces PML-RARA protein degradation via enhanced UBE2I-mediated sumoylation. Arsenic Trioxide 18-21 retinoic acid receptor alpha Homo sapiens 103-107 27030546-3 2016 Thus, we hypothesized that PCGF2 might play a role in ATO-induced PML-RARA degradation by interacting with UBE2I. Arsenic Trioxide 54-57 retinoic acid receptor alpha Homo sapiens 70-74 26728337-2 2016 PML and RARA mutations have been shown to directly respond to arsenic trioxide (ATO) and all-trans retinoic (ATRA). Arsenic Trioxide 62-78 retinoic acid receptor alpha Homo sapiens 8-12 26728337-2 2016 PML and RARA mutations have been shown to directly respond to arsenic trioxide (ATO) and all-trans retinoic (ATRA). Arsenic Trioxide 80-83 retinoic acid receptor alpha Homo sapiens 8-12 27089249-3 2016 In classic APL harboring PML-RARalpha transcripts, more than 90% of patients can achieve complete remission when treated with ATRA combined with arsenic trioxide chemotherapy. Arsenic Trioxide 145-161 retinoic acid receptor alpha Homo sapiens 29-37 27030546-6 2016 Moreover, overexpression of PCGF2 protected ATO-mediated degradation of ectopic and endogenous PML-RARA in 293T and NB4 cells, respectively. Arsenic Trioxide 44-47 retinoic acid receptor alpha Homo sapiens 99-103 27030546-10 2016 Intriguingly, upon ATO-treatment, such interaction was disrupted and UBE2I was co-immunoprecipitated or co-localized with its SUMO substrate, PML-RARA. Arsenic Trioxide 19-22 retinoic acid receptor alpha Homo sapiens 146-150 27030546-11 2016 Taken together, our results suggested a novel role of PCGF2 in ATO-mediated degradation of PML-RARA that PCGF2 might act as a negative regulator of UBE2I via direct interaction. Arsenic Trioxide 63-66 retinoic acid receptor alpha Homo sapiens 95-99 26537301-0 2016 Varying responses of PML-RARA with different genetic mutations to arsenic trioxide. Arsenic Trioxide 66-82 retinoic acid receptor alpha Homo sapiens 25-29 26537301-4 2016 Here we performed in vitro functional analyses and a retrospective analysis of APL patients to investigate the effect of PML-RARA mutations in mediating resistance to arsenic trioxide. Arsenic Trioxide 167-183 retinoic acid receptor alpha Homo sapiens 125-129 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. Arsenic Trioxide 57-73 retinoic acid receptor alpha Homo sapiens 141-149 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. Arsenic Trioxide 75-78 retinoic acid receptor alpha Homo sapiens 141-149 26294332-10 2015 This study demonstrated frequent mutations of PML-RARA and supported a clonal selection model in relation to APL relapse and ATO resistance. Arsenic Trioxide 125-128 retinoic acid receptor alpha Homo sapiens 50-54 26414475-4 2015 It is important to identify these cryptic and variant translocations because certain variants, including ZBTB16/RARA and STAT5B/RARA, are resistant to treatment with all-trans retinoic acid, arsenic trioxide, and anthracyclines. Arsenic Trioxide 191-207 retinoic acid receptor alpha Homo sapiens 112-116 27182481-4 2015 The identification of arsenic trioxide (ATO) as a valid therapy not only in relapsed patients but also as an alternative to standard therapy alone or in association with all-trans-retinoic acid enlarges the setting of validation of MRD evaluation in APL patients, considering a possible different clearance of PML-RARalpha with innovative therapy different from the standard ones. Arsenic Trioxide 40-43 retinoic acid receptor alpha Homo sapiens 314-322 27182481-4 2015 The identification of arsenic trioxide (ATO) as a valid therapy not only in relapsed patients but also as an alternative to standard therapy alone or in association with all-trans-retinoic acid enlarges the setting of validation of MRD evaluation in APL patients, considering a possible different clearance of PML-RARalpha with innovative therapy different from the standard ones. Arsenic Trioxide 22-38 retinoic acid receptor alpha Homo sapiens 314-322 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. Arsenic Trioxide 15-31 retinoic acid receptor alpha Homo sapiens 90-98 24720386-7 2014 RARA fusion proteins behave as potent transcriptional repressors of retinoic acid signalling, inducing a differentiation blockage at the promyelocyte stage which can be overcome with therapeutic doses of ATRA or arsenic trioxide. Arsenic Trioxide 212-228 retinoic acid receptor alpha Homo sapiens 0-4 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. Arsenic Trioxide 33-36 retinoic acid receptor alpha Homo sapiens 90-98 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. Arsenic Trioxide 111-127 retinoic acid receptor alpha Homo sapiens 35-39 25319615-5 2014 On the other hand, arsenic trioxide (ATO), another promising agent used to treat APL, directly binds to the PML moiety of the PML-RARalpha protein, causing oxidation and multimerization. Arsenic Trioxide 19-35 retinoic acid receptor alpha Homo sapiens 130-138 25319615-5 2014 On the other hand, arsenic trioxide (ATO), another promising agent used to treat APL, directly binds to the PML moiety of the PML-RARalpha protein, causing oxidation and multimerization. Arsenic Trioxide 37-40 retinoic acid receptor alpha Homo sapiens 130-138 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. Arsenic Trioxide 129-132 retinoic acid receptor alpha Homo sapiens 35-39 23208507-2 2013 In APL cells with PML/RARA fusions, arsenic trioxide and all-trans retinoic acid treatments specifically target the fusion protein for proteasome-dependent degradation, thereby promoting cellular differentiation and clinical remission of disease. Arsenic Trioxide 36-52 retinoic acid receptor alpha Homo sapiens 22-26 23469683-9 2013 ATO caused a profound decrease in the protein level of PML/RARalpha in NB4 cells after 48 h, but there was no change with AICAR and the combination. Arsenic Trioxide 0-3 retinoic acid receptor alpha Homo sapiens 59-67 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. Arsenic Trioxide 260-265 retinoic acid receptor alpha Homo sapiens 62-90 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. Arsenic Trioxide 260-265 retinoic acid receptor alpha Homo sapiens 92-100 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. Arsenic Trioxide 260-265 retinoic acid receptor alpha Homo sapiens 159-167 23670176-5 2013 The PML-B2 mutation interferes with the direct binding of As2O3 with PML-B2, and PML-RARalpha SUMOylation with As2O3 followed by multimerization and degradation is impaired. Arsenic Trioxide 111-116 retinoic acid receptor alpha Homo sapiens 85-93 23271512-0 2013 All-trans retinoic acid and arsenic trioxide resistance of acute promyelocytic leukemia with the variant STAT5B-RARA fusion gene. Arsenic Trioxide 28-44 retinoic acid receptor alpha Homo sapiens 112-116 22692509-7 2012 Thus, ATO may inhibit nuclear activities of PML and PML/RARA in postmitotic cells through CyPN-dependent cytoplasmic sequestration. Arsenic Trioxide 6-9 retinoic acid receptor alpha Homo sapiens 56-60 22406621-5 2012 In addition, PIAS1-mediated SUMOylation of PML-RARA was essential for induction of its degradation by arsenic trioxide, an effective APL treatment. Arsenic Trioxide 102-118 retinoic acid receptor alpha Homo sapiens 47-51 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. Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 139-147 22056243-0 2012 Curing APL through PML/RARA degradation by As2O3. Arsenic Trioxide 43-48 retinoic acid receptor alpha Homo sapiens 23-27 22056243-6 2012 As discussed below, arsenic binding, oxidation, sumoylation on PML nuclear bodies, and RNF4-mediated ubiquitination all contribute to the As(2)O(3)-triggered catabolism of PML/RARA. Arsenic Trioxide 138-147 retinoic acid receptor alpha Homo sapiens 176-180 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). Arsenic Trioxide 209-225 retinoic acid receptor alpha Homo sapiens 162-170 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). Arsenic Trioxide 227-230 retinoic acid receptor alpha Homo sapiens 162-170 21613260-0 2011 Missense mutations in PML-RARA are critical for the lack of responsiveness to arsenic trioxide treatment. Arsenic Trioxide 78-94 retinoic acid receptor alpha Homo sapiens 26-30 20615082-8 2010 In summary, our results indicate that ATO in conjunction with ATRA is of potential chemotherapeutic use in PML-RARalpha negative leukemias. Arsenic Trioxide 38-41 retinoic acid receptor alpha Homo sapiens 111-119 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. Arsenic Trioxide 35-51 retinoic acid receptor alpha Homo sapiens 133-137 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. Arsenic Trioxide 53-56 retinoic acid receptor alpha Homo sapiens 133-137 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). Arsenic Trioxide 84-100 retinoic acid receptor alpha Homo sapiens 277-305 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). Arsenic Trioxide 84-100 retinoic acid receptor alpha Homo sapiens 307-311 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. Arsenic Trioxide 47-63 retinoic acid receptor alpha Homo sapiens 275-279 20615082-1 2010 Arsenic trioxide (ATO) synergistically promotes all trans retinoic acid (ATRA)-induced differentiation of PML-RARalpha negative HL-60 myeloblastic leukemia cells. Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 110-118 20615082-1 2010 Arsenic trioxide (ATO) synergistically promotes all trans retinoic acid (ATRA)-induced differentiation of PML-RARalpha negative HL-60 myeloblastic leukemia cells. Arsenic Trioxide 18-21 retinoic acid receptor alpha Homo sapiens 110-118 20615082-2 2010 In PML-RARalpha positive myeloid leukemia cells, ATO is known to cause degradation of PML-RARalpha with subsequent induced myeloid differentiation. Arsenic Trioxide 49-52 retinoic acid receptor alpha Homo sapiens 7-15 20609355-0 2010 PML/RARA oxidation and arsenic binding initiate the antileukemia response of As2O3. Arsenic Trioxide 77-82 retinoic acid receptor alpha Homo sapiens 4-8 19468689-1 2010 Arsenic trioxide (ATO) is an inorganic arsenic derivative that is highly effective against PML-RARalpha-positive leukemia but much less against other hematological malignancies. Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 95-103 19468689-1 2010 Arsenic trioxide (ATO) is an inorganic arsenic derivative that is highly effective against PML-RARalpha-positive leukemia but much less against other hematological malignancies. Arsenic Trioxide 18-21 retinoic acid receptor alpha Homo sapiens 95-103 20378816-2 2010 Arsenic trioxide (As2O3) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells, PML-RARalpha (a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor alpha). Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 145-153 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. Arsenic Trioxide 28-44 retinoic acid receptor alpha Homo sapiens 65-69 20405253-0 2010 Relapsed APL patient with variant NPM-RARalpha fusion responded to arsenic trioxide-based therapy and achieved long-term survival. Arsenic Trioxide 67-83 retinoic acid receptor alpha Homo sapiens 38-46 20405253-2 2010 So far, there is a lack of information on the effectiveness of arsenic trioxide (ATO) in relapsed APL with variant RARalpha chimera including t(5;17)/NPM-RARalpha. Arsenic Trioxide 63-79 retinoic acid receptor alpha Homo sapiens 115-123 20405253-2 2010 So far, there is a lack of information on the effectiveness of arsenic trioxide (ATO) in relapsed APL with variant RARalpha chimera including t(5;17)/NPM-RARalpha. Arsenic Trioxide 81-84 retinoic acid receptor alpha Homo sapiens 115-123 20405253-3 2010 We report here a long-term survived APL patient with variant NPM-RARalpha fusion who relapsed four times and each time responded well to ATO or ATO-based re-induction therapy. Arsenic Trioxide 137-140 retinoic acid receptor alpha Homo sapiens 65-73 20405253-3 2010 We report here a long-term survived APL patient with variant NPM-RARalpha fusion who relapsed four times and each time responded well to ATO or ATO-based re-induction therapy. Arsenic Trioxide 144-147 retinoic acid receptor alpha Homo sapiens 65-73 20378816-0 2010 Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML. Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 46-54 20378816-2 2010 Arsenic trioxide (As2O3) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells, PML-RARalpha (a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor alpha). Arsenic Trioxide 18-23 retinoic acid receptor alpha Homo sapiens 145-153 18636556-4 2008 By using PR9, a sub-line of U937 stably transduced with the inducible PML/RARalpha expression vectors, we attributed disparities on ROS generation and ATO sensitivity to the occurrence of PML/RARalpha fusion protein, since PML/RARalpha-expressing cells appeared higher NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. Arsenic Trioxide 336-339 retinoic acid receptor alpha Homo sapiens 192-200 19815840-0 2010 Mobilization of PML/RARalpha negative peripheral blood stem cells with a combination of G-CSF and CXCR4 blockade in relapsed acute promyelocytic leukemia pre-treated with arsenic trioxide. Arsenic Trioxide 171-187 retinoic acid receptor alpha Homo sapiens 20-28 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. Arsenic Trioxide 35-51 retinoic acid receptor alpha Homo sapiens 138-142 19468269-3 2009 The use of all-trans-retinoic acid (ATRA) and arsenic trioxide, both of which induce degradation of the progressive multifocal leukoencephalopathy/retinoic acid receptor alpha oncoprotein, in combination with chemotherapy is currently the accepted treatment of APL, presenting a potential paradigm for differentiation therapy in clinical oncology. Arsenic Trioxide 46-62 retinoic acid receptor alpha Homo sapiens 147-175 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. Arsenic Trioxide 69-85 retinoic acid receptor alpha Homo sapiens 107-111 18636556-4 2008 By using PR9, a sub-line of U937 stably transduced with the inducible PML/RARalpha expression vectors, we attributed disparities on ROS generation and ATO sensitivity to the occurrence of PML/RARalpha fusion protein, since PML/RARalpha-expressing cells appeared higher NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. Arsenic Trioxide 151-154 retinoic acid receptor alpha Homo sapiens 192-200 18636556-4 2008 By using PR9, a sub-line of U937 stably transduced with the inducible PML/RARalpha expression vectors, we attributed disparities on ROS generation and ATO sensitivity to the occurrence of PML/RARalpha fusion protein, since PML/RARalpha-expressing cells appeared higher NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. Arsenic Trioxide 151-154 retinoic acid receptor alpha Homo sapiens 192-200 18636556-4 2008 By using PR9, a sub-line of U937 stably transduced with the inducible PML/RARalpha expression vectors, we attributed disparities on ROS generation and ATO sensitivity to the occurrence of PML/RARalpha fusion protein, since PML/RARalpha-expressing cells appeared higher NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. Arsenic Trioxide 336-339 retinoic acid receptor alpha Homo sapiens 192-200 18636556-7 2008 PML/RARalpha that bestows NB4 cells various pathological features, paradoxically also endows these cells with the basis for susceptibility to ATO-induced cytotoxcity. Arsenic Trioxide 142-145 retinoic acid receptor alpha Homo sapiens 4-12 18408733-1 2008 In acute promyelocytic leukaemia (APL), arsenic trioxide induces degradation of the fusion protein encoded by the PML-RARA oncogene, differentiation of leukaemic cells and produces clinical remissions. Arsenic Trioxide 40-56 retinoic acid receptor alpha Homo sapiens 118-122 17825229-0 2007 [Effects of arsenic trioxide and ATRA on PLZF-RARalpha-positive U937 leukemic cells]. Arsenic Trioxide 12-28 retinoic acid receptor alpha Homo sapiens 46-54 17825229-1 2007 AIM: To investigate effects of arsenic trioxide (As(2)O(3)) and alltrans retinoic acid (ATRA) on PLZF-RARalpha-positive cells. Arsenic Trioxide 31-47 retinoic acid receptor alpha Homo sapiens 102-110 17825229-1 2007 AIM: To investigate effects of arsenic trioxide (As(2)O(3)) and alltrans retinoic acid (ATRA) on PLZF-RARalpha-positive cells. Arsenic Trioxide 49-58 retinoic acid receptor alpha Homo sapiens 102-110 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. Arsenic Trioxide 198-201 retinoic acid receptor alpha Homo sapiens 31-39 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. Arsenic Trioxide 38-54 retinoic acid receptor alpha Homo sapiens 136-140 17018029-5 2006 DIDS (4,4"-diisothiocyanodihydrostilbene-2,2"-disulphonic acid) inhibited AE2 function, preventing the arsenic trioxide-induced degradation of RARalpha and low concentration showed synergistic effects on the expression of CD11c, which is related with cell differentiation. Arsenic Trioxide 103-119 retinoic acid receptor alpha Homo sapiens 143-151 16891316-1 2006 Arsenic trioxide (ATO) is a potent anti-leukemic chemotherapeutic agent for acute promyelocytic leukemia (APL) that results from a t (15, 17) chromosomal translocation that produces PML-RARalpha, a fusion protein between a tumor suppressor PML and the retinoic acid receptor RARalpha. Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 186-194 16891316-1 2006 Arsenic trioxide (ATO) is a potent anti-leukemic chemotherapeutic agent for acute promyelocytic leukemia (APL) that results from a t (15, 17) chromosomal translocation that produces PML-RARalpha, a fusion protein between a tumor suppressor PML and the retinoic acid receptor RARalpha. Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 275-283 16891316-1 2006 Arsenic trioxide (ATO) is a potent anti-leukemic chemotherapeutic agent for acute promyelocytic leukemia (APL) that results from a t (15, 17) chromosomal translocation that produces PML-RARalpha, a fusion protein between a tumor suppressor PML and the retinoic acid receptor RARalpha. Arsenic Trioxide 18-21 retinoic acid receptor alpha Homo sapiens 186-194 16891316-1 2006 Arsenic trioxide (ATO) is a potent anti-leukemic chemotherapeutic agent for acute promyelocytic leukemia (APL) that results from a t (15, 17) chromosomal translocation that produces PML-RARalpha, a fusion protein between a tumor suppressor PML and the retinoic acid receptor RARalpha. Arsenic Trioxide 18-21 retinoic acid receptor alpha Homo sapiens 275-283 16330433-2 2005 Here, we investigate whether these two agents influence the in vitro differentiation-inducing effect of arsenic trioxide (As2O3) on AML cells, an effective drug for the treatment of acute promyelocytic leukemia (APL) that is a unique subtype of AML with a specific fusion protein, PML-RARalpha. Arsenic Trioxide 104-120 retinoic acid receptor alpha Homo sapiens 285-293 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. Arsenic Trioxide 186-191 retinoic acid receptor alpha Homo sapiens 72-81 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. Arsenic Trioxide 186-191 retinoic acid receptor alpha Homo sapiens 90-99 16330433-9 2005 These two hypoxia-mimetic agents also accelerated As2O3-induced modulation and degradation of PML-RARalpha protein in NB4 cells. Arsenic Trioxide 50-55 retinoic acid receptor alpha Homo sapiens 98-106 16330433-11 2005 INTERPRETATION AND CONCLUSIONS: Mimicked hypoxia enhanced As2O3-induced differentiation, in which HIF-1alpha and PML/RARalpha proteins played an important role. Arsenic Trioxide 58-63 retinoic acid receptor alpha Homo sapiens 117-125 15592671-2 2005 We describe a patient with promyelocytic leukemia zinc finger/retinoic acid receptor alpha (PLZF/RARalpha) APML who was treated with combination chemotherapy after poor response to arsenic trioxide. Arsenic Trioxide 181-197 retinoic acid receptor alpha Homo sapiens 97-105 15781666-6 2005 Exposure to As2O3 decreased levels of PML-RARalpha in PR9 cells, and the combination of paricalcitol and As2O3 enhanced their monocytic differentiation in parallel with the As2O3-mediated decrease of PML-RARalpha. Arsenic Trioxide 12-17 retinoic acid receptor alpha Homo sapiens 42-50 15781666-6 2005 Exposure to As2O3 decreased levels of PML-RARalpha in PR9 cells, and the combination of paricalcitol and As2O3 enhanced their monocytic differentiation in parallel with the As2O3-mediated decrease of PML-RARalpha. Arsenic Trioxide 105-110 retinoic acid receptor alpha Homo sapiens 204-212 15781666-6 2005 Exposure to As2O3 decreased levels of PML-RARalpha in PR9 cells, and the combination of paricalcitol and As2O3 enhanced their monocytic differentiation in parallel with the As2O3-mediated decrease of PML-RARalpha. Arsenic Trioxide 105-110 retinoic acid receptor alpha Homo sapiens 204-212 15781666-9 2005 This probably occurred by As2O3 decreasing levels of both the repressive PML-RARalpha fusion protein and the vitamin D metabolizing protein, 25-hydroxyvitamin D3-24-hydroxylase, resulting in increased activity of paricalcitol. Arsenic Trioxide 26-31 retinoic acid receptor alpha Homo sapiens 77-85 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). Arsenic Trioxide 199-215 retinoic acid receptor alpha Homo sapiens 21-29 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. Arsenic Trioxide 41-46 retinoic acid receptor alpha Homo sapiens 159-167 15160934-6 2004 As2O3 treatment results in only complete degradation of PML-RARalpha protein in both ATRA-sensitive and -resistant APL cells. Arsenic Trioxide 0-5 retinoic acid receptor alpha Homo sapiens 60-68 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. Arsenic Trioxide 56-61 retinoic acid receptor alpha Homo sapiens 15-23 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. Arsenic Trioxide 56-61 retinoic acid receptor alpha Homo sapiens 134-142 14668793-8 2003 As2O3 differently altered IFN-induced gene products; it downregulated PML/RARalpha and PML, did not alter PKR and Stat1, and upregulated interferon regulatory family (IRF)-1. Arsenic Trioxide 0-5 retinoic acid receptor alpha Homo sapiens 74-82 11704854-0 2001 Pathways of retinoic acid- or arsenic trioxide-induced PML/RARalpha catabolism, role of oncogene degradation in disease remission. Arsenic Trioxide 30-46 retinoic acid receptor alpha Homo sapiens 59-67 14534537-3 2003 The response to As2O3 is genetically determined by the t(15;17)-or the t(9;22)-specific fusion proteins PML/RARalpha or BCR/ABL. Arsenic Trioxide 16-21 retinoic acid receptor alpha Homo sapiens 108-116 14534537-4 2003 The PML portion of PML/RARalpha is crucial for the sensitivity to As2O3. Arsenic Trioxide 66-71 retinoic acid receptor alpha Homo sapiens 23-31 14534537-9 2003 To disclose the mechanism of As2O3-induced apoptosis in PML/RARalpha- and BCR/ABL-expressing cells, we focused on the role of PML for As2O3-induced cell death. Arsenic Trioxide 29-34 retinoic acid receptor alpha Homo sapiens 60-77 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. Arsenic Trioxide 185-201 retinoic acid receptor alpha Homo sapiens 78-86 12429934-1 2002 Arsenic trioxide (As(2)O(3)) is highly effective in the treatment of acute promyelocytic leukemias that express the promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARalpha) fusion protein. Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 173-181 11413191-2 2001 In acute promyelocytic leukemia, PML/retinoic acid receptor (RAR) alpha expression disrupts NBs, but therapies such as retinoic acid or arsenic trioxide (As2O3) restore them. Arsenic Trioxide 154-159 retinoic acid receptor alpha Homo sapiens 61-64 11413191-4 2001 We demonstrate that As2O3 triggers the proteasome-dependent degradation of PML and PML/RARalpha and that this process requires a specific sumolation site in PML, K160. Arsenic Trioxide 20-25 retinoic acid receptor alpha Homo sapiens 87-95 11413191-8 2001 Therefore, studying the basis of As2O3-induced PML/RARalpha degradation we show that PML sumolation directly or indirectly promotes its catabolism, suggesting that mature NBs could be sites of intranuclear proteolysis and opening new insights into NB alterations found in viral infections or transformation. Arsenic Trioxide 33-38 retinoic acid receptor alpha Homo sapiens 51-59 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. Arsenic Trioxide 34-50 retinoic acid receptor alpha Homo sapiens 207-215 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. Arsenic Trioxide 52-61 retinoic acid receptor alpha Homo sapiens 207-215 11779431-7 2001 Both ATRA and As2O3 can also down-regulate the TF antigen in U937 cells transfected with or without PML-RARa. Arsenic Trioxide 14-19 retinoic acid receptor alpha Homo sapiens 104-108 11172537-4 2001 As2O3 over a wide range of concentrations (0.1 to 2.0 micromol/L) Induces degradation of PML-RARalpha as well as the wild-type PML and enhances the acetylation of histone, a process important for the transcriptional activation of genes. Arsenic Trioxide 0-5 retinoic acid receptor alpha Homo sapiens 93-101 11172537-9 2001 The in vivo effect of As2O3 seems to be related to the expression of APL-specific PML-RARalpha oncoprotein, and a synergistic effect between As2O3 and ATRA has been shown in the APL mouse model. Arsenic Trioxide 22-27 retinoic acid receptor alpha Homo sapiens 86-94 10910048-2 2000 In acute promyelocytic leukemia response to arsenic trioxide (As2O3) has been shown to be genetically determined by the acute promyelocytic leukemia-specific t(15;17) translocation product PML/RARalpha. Arsenic Trioxide 44-60 retinoic acid receptor alpha Homo sapiens 193-201 10910048-2 2000 In acute promyelocytic leukemia response to arsenic trioxide (As2O3) has been shown to be genetically determined by the acute promyelocytic leukemia-specific t(15;17) translocation product PML/RARalpha. Arsenic Trioxide 62-67 retinoic acid receptor alpha Homo sapiens 193-201 11798775-1 2000 OBJECTIVE: To illustrate the possible roles of acute promyelocytic leukemia-specific chimeric proteins PML-RARalpha and PLZF-RARalpha in the effects of arsenic trioxide (As(2)O(3)). Arsenic Trioxide 152-168 retinoic acid receptor alpha Homo sapiens 107-115 10830735-6 2000 As2O3 can induce partial differentiation and subsequent apoptosis of APL cells through degradation of wild type PML and PML/RAR alpha chimeric proteins and possible anti-mitochondrial effects. Arsenic Trioxide 0-5 retinoic acid receptor alpha Homo sapiens 120-133 11775865-8 2000 RA can potentiate As2O3-induced apoptosis even in RA-resistant HL-60 cells in which the classical ATRA response pathway is repressed owing to a homozygous inactivating mutation in the retinoic acid receptor alpha. Arsenic Trioxide 18-23 retinoic acid receptor alpha Homo sapiens 184-212 11798775-1 2000 OBJECTIVE: To illustrate the possible roles of acute promyelocytic leukemia-specific chimeric proteins PML-RARalpha and PLZF-RARalpha in the effects of arsenic trioxide (As(2)O(3)). Arsenic Trioxide 152-168 retinoic acid receptor alpha Homo sapiens 125-133 11798775-10 2000 CONCLUSION: PML-RARalpha and PLZF-RARalpha markedly enhance growth-inhibitory effects of As2)O3) on K562 cells. Arsenic Trioxide 89-95 retinoic acid receptor alpha Homo sapiens 16-24 11798775-10 2000 CONCLUSION: PML-RARalpha and PLZF-RARalpha markedly enhance growth-inhibitory effects of As2)O3) on K562 cells. Arsenic Trioxide 89-95 retinoic acid receptor alpha Homo sapiens 34-42 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. Arsenic Trioxide 87-103 retinoic acid receptor alpha Homo sapiens 119-127 10373566-0 1999 PIC-1/SUMO-1-modified PML-retinoic acid receptor alpha mediates arsenic trioxide-induced apoptosis in acute promyelocytic leukemia. Arsenic Trioxide 64-80 retinoic acid receptor alpha Homo sapiens 26-54 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. Arsenic Trioxide 105-110 retinoic acid receptor alpha Homo sapiens 119-127 10373566-6 1999 Taken together, these data provide novel insights into the mechanisms involved in As2O3-induced apoptosis in APL and predict that treatment of t(11;17) (PLZF-RARalpha-positive) APLs with As2O3 will not be successful. Arsenic Trioxide 82-87 retinoic acid receptor alpha Homo sapiens 158-166 10373566-6 1999 Taken together, these data provide novel insights into the mechanisms involved in As2O3-induced apoptosis in APL and predict that treatment of t(11;17) (PLZF-RARalpha-positive) APLs with As2O3 will not be successful. Arsenic Trioxide 187-192 retinoic acid receptor alpha Homo sapiens 158-166 9716575-0 1998 Arsenic trioxide and melarsoprol induce programmed cell death in myeloid leukemia cell lines and function in a PML and PML-RARalpha independent manner. Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 123-131 9716575-2 1998 As2O3 has been proposed to principally target PML and PML-RARalpha proteins in APL cells. Arsenic Trioxide 0-5 retinoic acid receptor alpha Homo sapiens 58-66 9716575-7 1998 As2O3 relocalized PML and PML-RARalpha onto nuclear bodies, which was followed by PML degradation in NB4 as well as in HL60 and U937 cell lines. Arsenic Trioxide 0-5 retinoic acid receptor alpha Homo sapiens 30-38 9596679-1 1998 In the acute promyelocytic leukemia (APL) cell line NB4, as well as in APL patients" cells, arsenic trioxide (As2O3) leads to incomplete cell maturation, induction of apoptosis, as well as to the degradation of the oncogenic PML/RARalpha fusion protein. Arsenic Trioxide 92-108 retinoic acid receptor alpha Homo sapiens 229-237 9596679-1 1998 In the acute promyelocytic leukemia (APL) cell line NB4, as well as in APL patients" cells, arsenic trioxide (As2O3) leads to incomplete cell maturation, induction of apoptosis, as well as to the degradation of the oncogenic PML/RARalpha fusion protein. Arsenic Trioxide 110-115 retinoic acid receptor alpha Homo sapiens 229-237 9596679-3 1998 When grown in the presence of As2O3, NB4-AsR cells degrade PML/RARalpha, slightly differentiate, and become more sensitive to serum deprivation-induced apoptosis. Arsenic Trioxide 30-35 retinoic acid receptor alpha Homo sapiens 63-71 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. Arsenic Trioxide 6-11 retinoic acid receptor alpha Homo sapiens 47-55 9450572-9 1998 As2O3 induces loss of the PML/RAR alpha fusion protein in NB4 cells, in retinoic-acid resistant cells derived from them, in fresh APL cells from patients, and in non-APL cells transfected to express this protein. Arsenic Trioxide 0-5 retinoic acid receptor alpha Homo sapiens 26-39 15622748-0 1997 [Effects of arsenic trioxide on the subcellular localization of PML/PML-RARalpha protein in leukemic cells]. Arsenic Trioxide 12-28 retinoic acid receptor alpha Homo sapiens 72-80 9535176-8 1997 Modulation and degradation of PML-RAR alpha proteins can be induced by As2O3 and probably contribute to these two effects. Arsenic Trioxide 71-76 retinoic acid receptor alpha Homo sapiens 34-37 9535176-9 1997 These studies lead to a model in which PML-RAR alpha could be the target of both ATRA differentiation therapy and As2O3 apoptosis therapy. Arsenic Trioxide 114-119 retinoic acid receptor alpha Homo sapiens 43-46 15622748-2 1997 METHODS: Effects of As2O3 on the subcellular localization of PML-RARalpha in NB4 cells were studied. Arsenic Trioxide 20-25 retinoic acid receptor alpha Homo sapiens 65-73 15622748-4 1997 CONCLUSION: As2O3-induced apoptosis was independent of the retinoic acid signal pathway, and it might be regulated by PML/PML-RARalpha and/or other related genes. Arsenic Trioxide 12-17 retinoic acid receptor alpha Homo sapiens 126-134 15622748-1 1997 OBJECTIVE: In order to illustrate the possible roles of PML-RARalpha protein in arsenic trioxide (AsO3)-induced NB4 cell apoptosis. Arsenic Trioxide 80-96 retinoic acid receptor alpha Homo sapiens 60-68 34938986-3 2021 The identification of a balanced reciprocal translocation between chromosomes 15 and 17, resulting in fusion between the promyelocytic leukemia gene and the retinoic acid receptor alpha, has been crucial in understanding the mechanisms of leukemogenesis, and responsible for the peculiar response to targeted therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Arsenic Trioxide 357-373 retinoic acid receptor alpha Homo sapiens 157-185 34348549-2 2022 The improvement of APL outcome is mainly due to two agents, which target the typical translocation t(15;17) and its fusion transcript PML-RARalpha responsible for initiating and maintaining the disease: all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Arsenic Trioxide 238-254 retinoic acid receptor alpha Homo sapiens 138-146 34348549-2 2022 The improvement of APL outcome is mainly due to two agents, which target the typical translocation t(15;17) and its fusion transcript PML-RARalpha responsible for initiating and maintaining the disease: all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Arsenic Trioxide 256-259 retinoic acid receptor alpha Homo sapiens 138-146 34310740-1 2021 Under the differentiation induction therapy with all-trans retinoic acid and arsenic trioxide, nearly 95% of typical acute promyelocyte leukemia (APL), which is characterized by the presence of PML-RARA, patients can be cured. Arsenic Trioxide 77-93 retinoic acid receptor alpha Homo sapiens 198-202 34938986-3 2021 The identification of a balanced reciprocal translocation between chromosomes 15 and 17, resulting in fusion between the promyelocytic leukemia gene and the retinoic acid receptor alpha, has been crucial in understanding the mechanisms of leukemogenesis, and responsible for the peculiar response to targeted therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Arsenic Trioxide 375-378 retinoic acid receptor alpha Homo sapiens 157-185 32455804-2 2020 Resistance to all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested in PLZF/RARalpha and other variant APLs. Arsenic Trioxide 49-65 retinoic acid receptor alpha Homo sapiens 99-107 35517404-0 2022 Arsenic trioxide induces proteasome dependent TBLR1-RARalpha degradation to improve leukemia eradication through cell differentiation enhancement. Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 52-60 35517404-3 2022 Here, we investigated the role and mechanism of TBLR1-RARalpha, a rare RARalpha fusion gene, on ATO treatment in leukemia cells. Arsenic Trioxide 96-99 retinoic acid receptor alpha Homo sapiens 54-62 35517404-4 2022 METHODS: By constructing two cell models of leukemia cell line HL-60 and U937 with overexpressed TBLR1-RARalpha, we detected the cell differentiation in the two cell models after ATO treatment by flow cytometry and Wright staining. Arsenic Trioxide 179-182 retinoic acid receptor alpha Homo sapiens 103-111 35517404-6 2022 RESULTS: We found that TBLR1-RARalpha enhanced ATO-induced apoptosis and cell proliferation inhibition. Arsenic Trioxide 47-50 retinoic acid receptor alpha Homo sapiens 29-37 35517404-7 2022 Besides, TBLR1-RARalpha also promoted ATO-induced cell differentiation. Arsenic Trioxide 38-41 retinoic acid receptor alpha Homo sapiens 15-23 35517404-8 2022 Furthermore, we found that the mitochondrial caspase pathway was involved in the apoptosis induced by ATO treatment in TBLR1-RARalpha positive leukemia cells. Arsenic Trioxide 102-105 retinoic acid receptor alpha Homo sapiens 125-133 35198449-4 2022 In this report, we identified THRAP3 as novel RARA fusion in resembling APL, which was resistant to all-trans retinoic acid (ATRA) combined arsenic trioxide (ATO) chemotherapy. Arsenic Trioxide 140-156 retinoic acid receptor alpha Homo sapiens 46-50 35198449-4 2022 In this report, we identified THRAP3 as novel RARA fusion in resembling APL, which was resistant to all-trans retinoic acid (ATRA) combined arsenic trioxide (ATO) chemotherapy. Arsenic Trioxide 158-161 retinoic acid receptor alpha Homo sapiens 46-50 32882258-3 2020 Arsenic trioxide (ATO) is one of the most common drugs used in the frontline treatment of APL that act through targeting and destabilizing the PML/RARalpha oncofusion protein. Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 147-155 32882258-3 2020 Arsenic trioxide (ATO) is one of the most common drugs used in the frontline treatment of APL that act through targeting and destabilizing the PML/RARalpha oncofusion protein. Arsenic Trioxide 18-21 retinoic acid receptor alpha Homo sapiens 147-155 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. Arsenic Trioxide 131-147 retinoic acid receptor alpha Homo sapiens 95-103 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. Arsenic Trioxide 149-154 retinoic acid receptor alpha Homo sapiens 95-103 35517404-10 2022 CONCLUSIONS: Our study provides evidence that TBLR1-RARalpha positive APL patients may benefit from ATO treatment, thereby improving the appropriate management in TBLR1-RARalpha positive APL. Arsenic Trioxide 100-103 retinoic acid receptor alpha Homo sapiens 52-60 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. Arsenic Trioxide 28-44 retinoic acid receptor alpha Homo sapiens 155-163 33091440-3 2020 Mechanistically, ATO can induce PML/RARalpha fusion protein degradation, causing APL cell differentiation and apoptosis. Arsenic Trioxide 17-20 retinoic acid receptor alpha Homo sapiens 36-44 32455804-2 2020 Resistance to all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested in PLZF/RARalpha and other variant APLs. Arsenic Trioxide 67-70 retinoic acid receptor alpha Homo sapiens 99-107 32223133-1 2020 Arsenic trioxide (ATO) is a therapeutic agents used to treat acute promyelocytic leukemia (APL), a disease caused by a chromosomal translocation of the retinoic acid receptor a (RARalpha) gene that can occur reciprocally with the promyelocytic leukemia (PML) gene. Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 178-186 32223133-1 2020 Arsenic trioxide (ATO) is a therapeutic agents used to treat acute promyelocytic leukemia (APL), a disease caused by a chromosomal translocation of the retinoic acid receptor a (RARalpha) gene that can occur reciprocally with the promyelocytic leukemia (PML) gene. Arsenic Trioxide 18-21 retinoic acid receptor alpha Homo sapiens 178-186 31214877-2 2019 It is reported that arsenicals can effectively degrade PML/RARalpha, such as arsenic trioxide and realgar. Arsenic Trioxide 77-93 retinoic acid receptor alpha Homo sapiens 59-67 32163072-4 2020 Here, we introduce in depth the latest evidence and detailed insights into ATO-mediated cures for APL by targeting PML/RARalpha chimeric protein, followed by the preclinical and clinical efficacy of ATO on various non-APL malignancies and solid tumors. Arsenic Trioxide 75-78 retinoic acid receptor alpha Homo sapiens 119-127 31670356-1 2019 Arsenic trioxide (As2O3) is one of the most effective drugs for the treatment of acute promyelocytic leukemia (APL), and induces the degradation of chimeric oncoprotein PML/RARalpha (P/R) and APL cell differentiation. Arsenic Trioxide 18-23 retinoic acid receptor alpha Homo sapiens 173-181 31670356-1 2019 Arsenic trioxide (As2O3) is one of the most effective drugs for the treatment of acute promyelocytic leukemia (APL), and induces the degradation of chimeric oncoprotein PML/RARalpha (P/R) and APL cell differentiation. Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 173-181 31083206-14 2019 LESSONS: Both STAT5b-RARalpha-positive APL and PLZF-RARalpha-positive APL appear to be resistant to both ATRA and ATO, so combined chemotherapy and allo-HSCT should be considered. Arsenic Trioxide 114-117 retinoic acid receptor alpha Homo sapiens 21-29 31083206-1 2019 RATIONALE: The vast majority of acute promyelocytic leukemia (APL) is characterized with a specific chromosomal translocation t (15, 17) (q22, q21), which fuses PML-RARalpha leading to a good response to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Arsenic Trioxide 239-255 retinoic acid receptor alpha Homo sapiens 165-173 31083206-1 2019 RATIONALE: The vast majority of acute promyelocytic leukemia (APL) is characterized with a specific chromosomal translocation t (15, 17) (q22, q21), which fuses PML-RARalpha leading to a good response to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Arsenic Trioxide 257-260 retinoic acid receptor alpha Homo sapiens 165-173 31083206-14 2019 LESSONS: Both STAT5b-RARalpha-positive APL and PLZF-RARalpha-positive APL appear to be resistant to both ATRA and ATO, so combined chemotherapy and allo-HSCT should be considered. Arsenic Trioxide 114-117 retinoic acid receptor alpha Homo sapiens 52-60 29159499-3 2018 Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARalpha induces cell cycle change and apoptosis. Arsenic Trioxide 0-16 retinoic acid receptor alpha Homo sapiens 93-101 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. Arsenic Trioxide 103-119 retinoic acid receptor alpha Homo sapiens 25-33 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. Arsenic Trioxide 121-124 retinoic acid receptor alpha Homo sapiens 25-33 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. Arsenic Trioxide 171-174 retinoic acid receptor alpha Homo sapiens 136-144 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. Arsenic Trioxide 82-98 retinoic acid receptor alpha Homo sapiens 14-18 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. Arsenic Trioxide 100-103 retinoic acid receptor alpha Homo sapiens 14-18 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. Arsenic Trioxide 124-140 retinoic acid receptor alpha Homo sapiens 221-225 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. Arsenic Trioxide 142-145 retinoic acid receptor alpha Homo sapiens 221-225 29159499-3 2018 Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARalpha induces cell cycle change and apoptosis. Arsenic Trioxide 18-21 retinoic acid receptor alpha Homo sapiens 93-101 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). Arsenic Trioxide 38-54 retinoic acid receptor alpha Homo sapiens 247-255 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. Arsenic Trioxide 120-125 retinoic acid receptor alpha Homo sapiens 89-97 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. Arsenic Trioxide 120-125 retinoic acid receptor alpha Homo sapiens 161-169 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). Arsenic Trioxide 220-236 retinoic acid receptor alpha Homo sapiens 132-140 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). Arsenic Trioxide 238-241 retinoic acid receptor alpha Homo sapiens 132-140 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. Arsenic Trioxide 49-65 retinoic acid receptor alpha Homo sapiens 125-133 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. Arsenic Trioxide 67-70 retinoic acid receptor alpha Homo sapiens 125-133 28492552-5 2017 Irf8, whose expression increased along with spontaneous differentiation of the APL progenitors in vivo, represented such a PML/RARalpha-dysregulated gene that was refractory to ATRA/ATO signaling. Arsenic Trioxide 182-185 retinoic acid receptor alpha Homo sapiens 127-135 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). Arsenic Trioxide 56-59 retinoic acid receptor alpha Homo sapiens 247-255 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. Arsenic Trioxide 113-116 retinoic acid receptor alpha Homo sapiens 145-153 28028657-0 2017 PML-RARA mutations confer varying arsenic trioxide resistance. Arsenic Trioxide 34-50 retinoic acid receptor alpha Homo sapiens 4-8 28129653-2 2017 All-trans retinoic acid (ATRA) and arsenic trioxide cure most patients by directly targeting PML-RARalpha. Arsenic Trioxide 35-51 retinoic acid receptor alpha Homo sapiens 97-105 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. Arsenic Trioxide 126-129 retinoic acid receptor alpha Homo sapiens 4-12