PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 22851953-3 2012 Topoisomerase II inhibitors, including etoposide and teniposide, frequently cause rearrangements involving the mixed lineage leukemia (MLL) gene on chromosome 11q23, which is associated with secondary leukemia. Etoposide 39-48 lysine methyltransferase 2A Homo sapiens 135-138 22851953-4 2012 The prognosis is extremely poor for leukemias associated with rearrangements in the MLL gene, including etoposide-related secondary leukemias. Etoposide 104-113 lysine methyltransferase 2A Homo sapiens 84-87 19587093-0 2009 Etoposide induces MLL rearrangements and other chromosomal abnormalities in human embryonic stem cells. Etoposide 0-9 lysine methyltransferase 2A Homo sapiens 18-21 21135858-5 2011 In fact, chronic exposure of human embryonic stem cells (hESCs) to etoposide induces MLL rearrangements and makes hESC more prone to acquire subsequent chromosomal abnormalities than postnatal CD34(+) cells, linking embryonic exposure to topoisomerase II inhibitors to genomic instability and MLL rearrangements. Etoposide 67-76 lysine methyltransferase 2A Homo sapiens 85-88 21135858-5 2011 In fact, chronic exposure of human embryonic stem cells (hESCs) to etoposide induces MLL rearrangements and makes hESC more prone to acquire subsequent chromosomal abnormalities than postnatal CD34(+) cells, linking embryonic exposure to topoisomerase II inhibitors to genomic instability and MLL rearrangements. Etoposide 67-76 lysine methyltransferase 2A Homo sapiens 293-296 19587093-10 2009 These data show that chronic exposure of developmentally early stem cells to etoposide induces MLL rearrangements and make hESCs more prone to acquire other chromosomal abnormalities than postnatal CD34(+) cells, linking embryonic genotoxic exposure to genomic instability. Etoposide 77-86 lysine methyltransferase 2A Homo sapiens 95-98 22615413-5 2012 We show that most etoposide-induced chromosome breaks in the MLL locus and the overall genotoxicity of etoposide are dependent on topoisomerase IIbeta, but that topoisomerase IIalpha and -beta occupancy and etoposide-induced DNA cleavage data suggest factors other than local topoisomerase II concentration determine specific clustering of MLL translocation breakpoints in t-AML. Etoposide 18-27 lysine methyltransferase 2A Homo sapiens 61-64 22615413-5 2012 We show that most etoposide-induced chromosome breaks in the MLL locus and the overall genotoxicity of etoposide are dependent on topoisomerase IIbeta, but that topoisomerase IIalpha and -beta occupancy and etoposide-induced DNA cleavage data suggest factors other than local topoisomerase II concentration determine specific clustering of MLL translocation breakpoints in t-AML. Etoposide 18-27 lysine methyltransferase 2A Homo sapiens 340-343 22615413-5 2012 We show that most etoposide-induced chromosome breaks in the MLL locus and the overall genotoxicity of etoposide are dependent on topoisomerase IIbeta, but that topoisomerase IIalpha and -beta occupancy and etoposide-induced DNA cleavage data suggest factors other than local topoisomerase II concentration determine specific clustering of MLL translocation breakpoints in t-AML. Etoposide 103-112 lysine methyltransferase 2A Homo sapiens 340-343 22615413-5 2012 We show that most etoposide-induced chromosome breaks in the MLL locus and the overall genotoxicity of etoposide are dependent on topoisomerase IIbeta, but that topoisomerase IIalpha and -beta occupancy and etoposide-induced DNA cleavage data suggest factors other than local topoisomerase II concentration determine specific clustering of MLL translocation breakpoints in t-AML. Etoposide 103-112 lysine methyltransferase 2A Homo sapiens 340-343 21048951-4 2010 Chromosome translocations involving the MLL gene on 11q23 are the most frequent chromosome abnormalities in secondary leukemias associated with chemotherapy employing etoposide, a topoisomerase II poison. Etoposide 167-176 lysine methyltransferase 2A Homo sapiens 40-43 19587093-5 2009 We addressed whether: (i) low doses of etoposide promote MLL rearrangements in hESCs and hESCs-derived hematopoietic cells; (ii) MLL rearrangements are sufficient to confer hESCs with a selective growth advantage and (iii) continuous exposure to low doses of etoposide induces hESCs to acquire other chromosomal abnormalities. Etoposide 39-48 lysine methyltransferase 2A Homo sapiens 57-60 19587093-7 2009 Etoposide induced MLL rearrangements in hESCs and their hematopoietic derivatives. Etoposide 0-9 lysine methyltransferase 2A Homo sapiens 18-21 21637660-0 2009 Preferential induction of MLL(Mixed Lineage Leukemia) rearrangements in human lymphocyte cultures treated with etoposide. Etoposide 111-120 lysine methyltransferase 2A Homo sapiens 26-29 21637660-7 2009 This greater susceptibility to etoposide-induced cleavage may explain the more frequent involvement of MLL in treatment-related leukemia. Etoposide 31-40 lysine methyltransferase 2A Homo sapiens 103-106 18774953-0 2008 Etoposide-initiated MLL rearrangements: the pitfalls of inverse PCR. Etoposide 0-9 lysine methyltransferase 2A Homo sapiens 20-23 18509329-6 2008 Moreover, in 25 cell lines, etoposide-induced MLL fusions did not differ in sensitive vs. resistant lines at equitoxic concentrations (P = 0.65). Etoposide 28-37 lysine methyltransferase 2A Homo sapiens 46-49 17332306-6 2007 RESULTS: We found that etoposide and the Hsp90/FLT3 inhibitor 17-AAG, had synergistic inhibitory effects on FLT3(+) MLL-fusion gene leukemia cells. Etoposide 23-32 lysine methyltransferase 2A Homo sapiens 116-119 18510699-1 2008 Rearrangements initiating within the well-characterized break-point cluster region of the mixed lineage leukemia (MLL) gene on 11q23 are a hallmark of therapy-related leukemias following treatment with topoisomerase II poisons including etoposide. Etoposide 237-246 lysine methyltransferase 2A Homo sapiens 114-117 18510699-3 2008 Although etoposide treatment is sufficient to induce readily detectable MLL rearrangements in primary human CD34+ cells, the majority of cells that gain translocations do not proliferate in culture possibly due to reduced proliferative capacity of most CD34+ cells during normal differentiation [Blood 2005;105:2124]. Etoposide 9-18 lysine methyltransferase 2A Homo sapiens 72-75 18510699-6 2008 Similar to results in CD34+ cells, a significant proportion of etoposide-treated HSC-derived clones harbored stable MLL rearrangements, including duplications, inversions and translocations. Etoposide 63-72 lysine methyltransferase 2A Homo sapiens 116-119 18510699-7 2008 These results indicate HSC are highly susceptible to etoposide-induced and potentially oncogenic rearrangements initiating within MLL, and these HSC are particularly proficient for continued long-term proliferation both in vivo and in vitro. Etoposide 53-62 lysine methyltransferase 2A Homo sapiens 130-133 17673902-1 2007 The genetic risk factors for etoposide-induced leukemia with MLL translocations remain largely unknown. Etoposide 29-38 lysine methyltransferase 2A Homo sapiens 61-64 18510699-0 2008 Etoposide-initiated MLL rearrangements detected at high frequency in human primitive hematopoietic stem cells with in vitro and in vivo long-term repopulating potential. Etoposide 0-9 lysine methyltransferase 2A Homo sapiens 20-23 16377807-0 2006 MLL rearrangements are induced by low doses of etoposide in human fetal hematopoietic stem cells. Etoposide 47-56 lysine methyltransferase 2A Homo sapiens 0-3 16809075-0 2006 Etoposide and illegitimate DNA double-strand break repair in the generation of MLL translocations: new insights and new questions. Etoposide 0-9 lysine methyltransferase 2A Homo sapiens 79-82 16809075-10 2006 There is a clear clinical association between previous exposure to etoposide and therapy-related acute myeloid leukemia (t-AML) characterized by chromosomal rearrangements involving the mixed lineage leukemia (MLL) gene on chromosome band 11q23 [C.A. Etoposide 67-76 lysine methyltransferase 2A Homo sapiens 210-213 16377807-8 2006 Immunophenotyping of MLL translocations revealed a significant increase in positive flow cytometry events at low etoposide concentrations and were consistent with MLL recombination. Etoposide 113-122 lysine methyltransferase 2A Homo sapiens 21-24 16377807-11 2006 Our data indicate that low acute doses of etoposide can cause DNA strand breaks and chromosomal rearrangements involving MLL in human fetal HSC. Etoposide 42-51 lysine methyltransferase 2A Homo sapiens 121-124 16434323-0 2006 Genotoxicity of etoposide: greater susceptibility of MLL than other target genes. Etoposide 16-25 lysine methyltransferase 2A Homo sapiens 53-56 16434323-3 2006 The effects of etoposide on the MLL, RUNX1, and MLLT3 genes were simultaneously studied in the same hemopoietic cell population. Etoposide 15-24 lysine methyltransferase 2A Homo sapiens 32-35 16434323-4 2006 We found MLL to be more susceptible to etoposide-induced cleavage than RUNX1 and MLLT3, with maximum cleavage at a lower drug concentration. Etoposide 39-48 lysine methyltransferase 2A Homo sapiens 9-12 15528316-8 2005 Thus, etoposide promotes specific rearrangements of MLL consistent with the full spectrum of oncogenic events identified in leukemic samples. Etoposide 6-15 lysine methyltransferase 2A Homo sapiens 52-55 15528316-0 2005 Therapy-related acute myeloid leukemia-like MLL rearrangements are induced by etoposide in primary human CD34+ cells and remain stable after clonal expansion. Etoposide 78-87 lysine methyltransferase 2A Homo sapiens 44-47 15528316-1 2005 Rearrangements involving the MLL gene on chromosome band 11q23 are a hallmark of therapy-related acute myeloid leukemias following treatment with topoisomerase II poisons including etoposide. Etoposide 181-190 lysine methyltransferase 2A Homo sapiens 29-32 15528316-3 2005 Repair of etoposide-stabilized DNA topoisomerase II covalent complexes may initiate MLL rearrangements observed in patients. Etoposide 10-19 lysine methyltransferase 2A Homo sapiens 84-87 15528316-4 2005 We used a culture system of primary human hematopoietic CD34+ cells and inverse polymerase chain reaction to characterize the spectrum of stable genomic rearrangements promoted by etoposide exposure originating within an MLL translocation hotspot in therapy-related leukemia. Etoposide 180-189 lysine methyltransferase 2A Homo sapiens 221-224 15319341-2 2004 The cytochrome P450 (P450)-derived catechol and quinone metabolites of etoposide may be important in the damage to the MLL (mixed lineage leukemia) gene and other genes resulting in leukemia-associated chromosomal translocations. Etoposide 71-80 lysine methyltransferase 2A Homo sapiens 119-122 14742315-3 2004 We show that a 399 bp fragment from the MLL bcr is sufficient to cause a 3-4-fold stimulation of spontaneously occurring DNA exchange and to respond to etoposide by up to 10-fold further elevated frequencies, i.e. to mimic the fragility of the 8.3 kb bcr during chemotherapy. Etoposide 152-161 lysine methyltransferase 2A Homo sapiens 40-43 14742315-5 2004 Consistent with the proposed role of p53 as a suppressor of error-prone recombination, both p53 proteins down-regulated recombination with most of the sequences tested, even with the MLL bcr after etoposide treatment. Etoposide 197-206 lysine methyltransferase 2A Homo sapiens 183-186 14990976-6 2004 Our results demonstrate a dosage-dependent effect of MLL-AF4 fusion oncoprotein on cell cycle progression, with increasing expression levels resulting in the accumulation in G1, prolonged doubling time, both findings that might be responsible for the increased resistance to etoposide-mediated cytotoxicity. Etoposide 275-284 lysine methyltransferase 2A Homo sapiens 53-56 14630694-4 2004 The fusion points in Mll chimeric products induced by etoposide were localized to a 1.5 kb region between exons 9 and 11, analogous to the MLL breakpoint cluster region in human leukemia. Etoposide 54-63 lysine methyltransferase 2A Homo sapiens 21-24 14970849-1 2004 Rearrangements of the ALL-1/MLL1 gene underlie the majority of infant acute leukaemias, as well as of therapy-related leukaemias developing in cancer patients treated with inhibitors of topoisomerase II, such as VP16 and doxorubicin. Etoposide 212-216 lysine methyltransferase 2A Homo sapiens 28-32 14630694-4 2004 The fusion points in Mll chimeric products induced by etoposide were localized to a 1.5 kb region between exons 9 and 11, analogous to the MLL breakpoint cluster region in human leukemia. Etoposide 54-63 lysine methyltransferase 2A Homo sapiens 139-142 11473400-1 2001 The anticancer drug etoposide is associated with leukemias with MLL gene translocations and other translocations as a treatment complication. Etoposide 20-29 lysine methyltransferase 2A Homo sapiens 64-67 14627986-3 2003 Etoposide-, etoposide metabolite- and doxorubicin-induced DNA topoisomerase II cleavage was examined in normal homologues of the MLL and AF-9 breakpoint sequences using an in vitro assay. Etoposide 0-9 lysine methyltransferase 2A Homo sapiens 129-132 11406628-1 2001 VP-16 (etoposide) has recently been shown to induce topoisomerase II (TOP2)-mediated DNA cleavage within the mixed lineage leukemia (MLL) breakpoint cluster region (bcr), suggesting a role of TOP2 in MLL gene rearrangement. Etoposide 0-5 lysine methyltransferase 2A Homo sapiens 133-136 11406628-1 2001 VP-16 (etoposide) has recently been shown to induce topoisomerase II (TOP2)-mediated DNA cleavage within the mixed lineage leukemia (MLL) breakpoint cluster region (bcr), suggesting a role of TOP2 in MLL gene rearrangement. Etoposide 0-5 lysine methyltransferase 2A Homo sapiens 200-203 11406628-1 2001 VP-16 (etoposide) has recently been shown to induce topoisomerase II (TOP2)-mediated DNA cleavage within the mixed lineage leukemia (MLL) breakpoint cluster region (bcr), suggesting a role of TOP2 in MLL gene rearrangement. Etoposide 7-16 lysine methyltransferase 2A Homo sapiens 133-136 11406628-1 2001 VP-16 (etoposide) has recently been shown to induce topoisomerase II (TOP2)-mediated DNA cleavage within the mixed lineage leukemia (MLL) breakpoint cluster region (bcr), suggesting a role of TOP2 in MLL gene rearrangement. Etoposide 7-16 lysine methyltransferase 2A Homo sapiens 200-203 11313693-4 2001 These observations suggest that clonal rearrangement of the MLL gene is caused by etoposide. Etoposide 82-91 lysine methyltransferase 2A Homo sapiens 60-63 11170441-0 2001 Etoposide metabolites enhance DNA topoisomerase II cleavage near leukemia-associated MLL translocation breakpoints. Etoposide 0-9 lysine methyltransferase 2A Homo sapiens 85-88 11170441-10 2001 Not only etoposide, but also its metabolites, enhance DNA topoisomerase II cleavage near MLL translocation breakpoints in in vitro assays. Etoposide 9-18 lysine methyltransferase 2A Homo sapiens 89-92 9199342-3 1997 We recently identified a unique site within the MLL bcr that is highly susceptible to DNA double-strand cleavage by classic topo II inhibitors (e.g., etoposide and doxorubicin). Etoposide 150-159 lysine methyltransferase 2A Homo sapiens 48-51 10758153-3 2000 The MLL BCR DNA cleavage was shown in primary progenitor hematopoietic cells from healthy newborns and adults as well as in cell lines; it colocalized with the MLL BCR cleavage site induced by chemotherapeutic agents, such as etoposide (VP16) and doxorubicin (Dox). Etoposide 226-235 lysine methyltransferase 2A Homo sapiens 4-7 10758153-3 2000 The MLL BCR DNA cleavage was shown in primary progenitor hematopoietic cells from healthy newborns and adults as well as in cell lines; it colocalized with the MLL BCR cleavage site induced by chemotherapeutic agents, such as etoposide (VP16) and doxorubicin (Dox). Etoposide 226-235 lysine methyltransferase 2A Homo sapiens 160-163 10758153-3 2000 The MLL BCR DNA cleavage was shown in primary progenitor hematopoietic cells from healthy newborns and adults as well as in cell lines; it colocalized with the MLL BCR cleavage site induced by chemotherapeutic agents, such as etoposide (VP16) and doxorubicin (Dox). Etoposide 237-241 lysine methyltransferase 2A Homo sapiens 4-7 10758153-3 2000 The MLL BCR DNA cleavage was shown in primary progenitor hematopoietic cells from healthy newborns and adults as well as in cell lines; it colocalized with the MLL BCR cleavage site induced by chemotherapeutic agents, such as etoposide (VP16) and doxorubicin (Dox). Etoposide 237-241 lysine methyltransferase 2A Homo sapiens 160-163 10758153-6 2000 Reversibility experiments demonstrated a religation of the bioflavonoid as well as the VP16-induced MLL cleavage site. Etoposide 87-91 lysine methyltransferase 2A Homo sapiens 100-103 8960661-3 1996 He developed AML (M4) in February 1993 after long-term treatment with oral etoposide (total dose 14,650 mg) t(9; 11) (p21; q23) with rearrangement of MLL genes was recognized. Etoposide 75-84 lysine methyltransferase 2A Homo sapiens 150-153 7948964-0 1994 Acute myelomonocytic leukemia after treatment with chronic oral etoposide: are MLL and LTG9 genes targets for etoposide? Etoposide 64-73 lysine methyltransferase 2A Homo sapiens 79-82 7948964-0 1994 Acute myelomonocytic leukemia after treatment with chronic oral etoposide: are MLL and LTG9 genes targets for etoposide? Etoposide 110-119 lysine methyltransferase 2A Homo sapiens 79-82 34034210-2 2021 These compounds (e.g. etoposide) promote DNA damage and are associated with KMT2A rearrangements. Etoposide 22-31 lysine methyltransferase 2A Homo sapiens 76-81 27813122-7 2017 Evidence for the downstream TopoII-independent mutagenic potential of Que was obtained by documenting further increased frequencies of MLL rearrangements in human HSPCs concomitantly treated with Etoposide and Que versus single treatments. Etoposide 196-205 lysine methyltransferase 2A Homo sapiens 135-138 27913458-2 2016 Treatment with epipodophyllotoxins like etoposide has been associated with a short interval between treatment and development of t-AML, with fusion oncogenes like KMT2A/MLL-MLLT3 and a better prognosis. Etoposide 40-49 lysine methyltransferase 2A Homo sapiens 163-168 27974636-6 2017 This is a significant finding because TOP2B has been linked to genetic damage associated with leukemic transformation, including etoposide-induced chromosomal breaks at the MLL and RUNX1 loci. Etoposide 129-138 lysine methyltransferase 2A Homo sapiens 173-176 32216001-7 2020 In the etoposide-treated cells, variable-sized rearrangement bands were detected in the RUNX1 and MLL genes at 3 h of culture, which decreased after 7 days. Etoposide 7-16 lysine methyltransferase 2A Homo sapiens 98-101 30387535-4 2019 Overlap of MLL bcr sequences associated with both infant acute leukemia and therapy-related leukemia following exposure to the topoisomerase II inhibitor etoposide led to the hypothesis that exposure during pregnancy to biochemically similar compounds may promote infant acute leukemia. Etoposide 154-163 lysine methyltransferase 2A Homo sapiens 11-14 30387535-6 2019 We show bioflavonoids genistein and quercetin most biochemically similar to etoposide have a strong association with MLL-AF9 bcr translocations, while kaempferol, fisetin, flavone, and myricetin have a weak but consistent association, and other compounds have a minimal association in both embryonic stem (ES) and hematopoietic stem cell (HSC) populations. Etoposide 76-85 lysine methyltransferase 2A Homo sapiens 117-120 32300400-5 2017 Patients with MLL- and CDKN2A-positive DLBCL may benefit from therapy with a dose-adjusted regimen of rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) compared to traditional rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). Etoposide 113-122 lysine methyltransferase 2A Homo sapiens 14-17 27119507-4 2016 It has been suggested that MLL fusions render cells susceptible to additional chromosomal damage upon exposure to etoposide. Etoposide 114-123 lysine methyltransferase 2A Homo sapiens 27-30 27473573-4 2016 CASE PRESENTATION: We report a case of acquired EBV-triggered HLH with progression to t-AML following etoposide therapy with cytogenetic abnormality for t (11; 19) (q23; p13) resulting in MLL gene fusion. Etoposide 102-111 lysine methyltransferase 2A Homo sapiens 188-191 26657054-1 2015 Etoposide, a topoisomerase 2 (TOP2) inhibitor, is associated with the development of KMT2A (MLL)-rearranged infant leukemia. Etoposide 0-9 lysine methyltransferase 2A Homo sapiens 85-90 26657054-1 2015 Etoposide, a topoisomerase 2 (TOP2) inhibitor, is associated with the development of KMT2A (MLL)-rearranged infant leukemia. Etoposide 0-9 lysine methyltransferase 2A Homo sapiens 92-95 26657054-3 2015 The present study examined the mechanism underlying the development of KMT2A (MLL)-rearranged infant leukemia in response to in utero exposure to etoposide in a mouse model. Etoposide 146-155 lysine methyltransferase 2A Homo sapiens 71-76 26657054-3 2015 The present study examined the mechanism underlying the development of KMT2A (MLL)-rearranged infant leukemia in response to in utero exposure to etoposide in a mouse model. Etoposide 146-155 lysine methyltransferase 2A Homo sapiens 78-81 24858818-8 2014 Notably, SYC-522 treatment significantly increased the sensitivity of MLL-rearranged leukemia cells to chemotherapeutics, such as mitoxantrone, etoposide and cytarabine. Etoposide 144-153 lysine methyltransferase 2A Homo sapiens 70-73 24766193-2 2014 Despite its wide clinical use, 2-3% of patients treated with etoposide eventually develop treatment-related acute myeloid leukemias (t-AMLs) characterized by rearrangements of the MLL gene. Etoposide 61-70 lysine methyltransferase 2A Homo sapiens 180-183 24086652-0 2013 The broken MLL gene is frequently located outside the inherent chromosome territory in human lymphoid cells treated with DNA topoisomerase II poison etoposide. Etoposide 149-158 lysine methyltransferase 2A Homo sapiens 11-14 24086652-5 2013 It was demonstrated that exposure of human Jurkat cells to etoposide resulted in frequent cleavage of MLL genes. Etoposide 59-68 lysine methyltransferase 2A Homo sapiens 102-105 24086652-7 2013 Using confocal microscopy and 3D modelling, we demonstrated that in cells treated with etoposide and cultivated for 1 h under normal conditions, ~9% of the broken MLL alleles were present outside the chromosome 11 territory, whereas in both control cells and cells inspected immediately after etoposide treatment, virtually all MLL alleles were present within the chromosomal territory. Etoposide 87-96 lysine methyltransferase 2A Homo sapiens 163-166 24086652-7 2013 Using confocal microscopy and 3D modelling, we demonstrated that in cells treated with etoposide and cultivated for 1 h under normal conditions, ~9% of the broken MLL alleles were present outside the chromosome 11 territory, whereas in both control cells and cells inspected immediately after etoposide treatment, virtually all MLL alleles were present within the chromosomal territory. Etoposide 87-96 lysine methyltransferase 2A Homo sapiens 328-331