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Most of the translocations disrupt a breakpoint cluster region (bcr) of the <jats:italic>MLL<\/jats:italic> gene at chromosome band 11q23. Other characteristic translocations also may occur. The normal function of the nuclear enzyme DNA topoisomerase II is to catalyze changes in DNA topology between relaxed and supercoiled states by transiently cleaving and re\u2010ligating both strands of the double helix. Anticancer drugs that are DNA topoisomerase II inhibitors are cytotoxic because they form complexes with DNA and DNA topoisomerase II. The complexes decrease the re\u2010ligation rate, disrupt the cleavage\u2010re\u2010ligation equilibrium, and have a net effect of increasing cleavage. The increased cleavage damages the DNA and leads to chromosomal breakage. Cells with irreparable DNA damage die by apoptosis. The association of DNA topoisomerase II inhibitors with leukemia suggests that the drug\u2010induced, DNA topoisomerase II\u2010mediated chromosomal breakage may be relevant to translocations in addition to this anti\u2010neoplastic, cytotoxic action. Epidemiological studies, genomic translocation breakpoint cloning and in vitro DNA topoisomerase II cleavage assays together lead to a model for treatment\u2010related leukemia in which DNA topoisomerase II causes chromosomal breakage and translocations form when the breakage is repaired. Med. Pediatr. Oncol. 36:525\u2013535, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mpo.1125","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T20:24:15Z","timestamp":1030307055000},"page":"525-535","source":"Crossref","is-referenced-by-count":149,"title":["Leukemias related to treatment with DNA topoisomerase II inhibitors*"],"prefix":"10.1002","volume":"36","author":[{"given":"Carolyn A.","family":"Felix","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,4,13]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/88.7.407"},{"key":"e_1_2_1_3_2","first-page":"645","article-title":"Patterns of second cancers","volume":"38","author":"Boice JD","year":"1997","journal-title":"Proc AACR"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.2950130112"},{"key":"e_1_2_1_5_2","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1200\/JCO.1986.4.10.1518","article-title":"Translocation (9;11)(p21q23) in a child with acute monoblastic leukemia following 2 1\/2 years after successful chemotherapy for neuroblastoma","volume":"4","author":"Weh HJ","year":"1986","journal-title":"J Clin Oncol"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V70.5.1412.1412"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/85.7.554"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.2950230205"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.2.569"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199112123252402"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)91956-B"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198907203210302"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1993.11.2.209"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1984.2.5.385"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(86)90388-8"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.2870020110"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.2950200110"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.2950230206"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-110-9-740"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19910801)68:3<600::AID-CNCR2820680326>3.0.CO;2-F"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)91465-K"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)92294-C"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.304.6832.951"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V76.6.1083.1083"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/85.1.36"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/85.1.60"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)90490-G"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)92133-M"},{"key":"e_1_2_1_29_2","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1093\/ajcp\/79.1.122","article-title":"Acute leukemia after successful chemotherapy for oat cell carcinoma","volume":"79","author":"Rose VL","year":"1983","journal-title":"Am J Clin Pathol"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1993.11.9.1703"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.16.8732"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.11.3945"},{"key":"e_1_2_1_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400576"},{"key":"e_1_2_1_34_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1992.10.1.156"},{"key":"e_1_2_1_35_2","first-page":"1305","article-title":"Molecular analysis of 13 cases of MLL\/11q23 secondary acute leukemia and identification of topoisomerase II consensus binding sequences near the chromosomal breakpoint of a secondary leukemia with the t(4;11)","volume":"9","author":"Domer PH","year":"1995","journal-title":"Leukemia"},{"key":"e_1_2_1_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.21.11583"},{"key":"e_1_2_1_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400769"},{"key":"e_1_2_1_38_2","volume-title":"IARC Monographs on the evaluation of carcinogenic risks to humans. 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