{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T06:49:09Z","timestamp":1696661349056},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,12,5]],"date-time":"2013-12-05T00:00:00Z","timestamp":1386201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:p>Genomic characterization of translocation breakpoints is relevant to identify possible mechanisms underlying their origin. The consistent association of anthracylines (e.g., epirubicin and idarubicin) in inducing therapy\u2010related acute leukemias (t\u2010AL) with mixed lineage leukemia (<jats:italic>MLL<\/jats:italic>) gene rearrangement suggests that <jats:italic>MLL<\/jats:italic> translocations are causative events for t\u2010AL. Using asymmetric multiplex PCR strategy followed by direct DNA sequencing, we characterized the genomic breakpoints of the <jats:italic>MLL<\/jats:italic> and <jats:italic>AFF1<\/jats:italic> genes in two patients who developed t\u2010AL with t(4;11)(q21;q23). Chemotherapeutic treatment of the primary disease in both patients included topoisomerase II (topo II) targeting agents. In one case, the <jats:italic>MLL<\/jats:italic> breakpoint was located in intron 9 at nucleotide position chr11:118354284 while the <jats:italic>AFF1<\/jats:italic> breakpoint was in intron 3 at nucleotide position chr4:87992070. The breakpoint junction sequences revealed an insertion of two nucleotides at the <jats:italic>MLL\u2010AFF1<\/jats:italic> junction. In the other patient, the <jats:italic>MLL<\/jats:italic> breakpoint was located in intron 11 at nucleotide position chr11:118359130\u201032 and the <jats:italic>AFF1<\/jats:italic> break was in intron 3 at nucleotide position chr4:87996215\u201017. The <jats:italic>MLL<\/jats:italic> breakpoint found in the latter patient was identical to that of two previously reported cases, strongly suggesting the presence of a preferential site of DNA cleavage in the presence of topo II inhibitor. In addition, microhomologies at the breakpoint junctions were indicative of DNA repair by the non\u2010homologous end joining (NHEJ) pathway. This study further supports the evidence that <jats:italic>MLL<\/jats:italic> breakpoints in therapy\u2010related acute leukemia with <jats:italic>MLL\u2010AFF1<\/jats:italic> are clustered in the telomeric half of the breakpoint cluster region that contains topo II recognition sites. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.22135","type":"journal-article","created":{"date-parts":[[2013,12,6]],"date-time":"2013-12-06T05:16:43Z","timestamp":1386307003000},"page":"248-254","source":"Crossref","is-referenced-by-count":5,"title":["Clustering of genomic breakpoints at the <i>MLL<\/i> locus in therapy\u2010related acute leukemia with t(4;11)(q21;q23)"],"prefix":"10.1002","volume":"53","author":[{"given":"Syed Khizer","family":"Hasan","sequence":"first","affiliation":[{"name":"Department of Biomedicine and Prevention University of Tor Vergata Rome Italy"},{"name":"Laboratorio di Neuro\u2010Oncoematologia Fondazione Santa Lucia Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Barba","sequence":"additional","affiliation":[{"name":"Hematology Unit University of Perugia Polo Unico S.M. Misericordia Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Metzler","sequence":"additional","affiliation":[{"name":"Department of Paediatrics University of Erlangen\u2010Nuremberg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariadomenica","family":"Divona","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention University of Tor Vergata Rome Italy"},{"name":"Laboratorio di Neuro\u2010Oncoematologia Fondazione Santa Lucia Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"Ottone","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention University of Tor Vergata Rome Italy"},{"name":"Laboratorio di Neuro\u2010Oncoematologia Fondazione Santa Lucia Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Cicconi","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention University of Tor Vergata Rome Italy"},{"name":"Laboratorio di Neuro\u2010Oncoematologia Fondazione Santa Lucia Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brunangelo","family":"Falini","sequence":"additional","affiliation":[{"name":"Institute of Hematology University of Perugia Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Mecucci","sequence":"additional","affiliation":[{"name":"Hematology Unit University of Perugia Polo Unico S.M. Misericordia Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Lo\u2010Coco","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention University of Tor Vergata Rome Italy"},{"name":"Laboratorio di Neuro\u2010Oncoematologia Fondazione Santa Lucia Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,12,5]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1182\/blood.V87.7.2649.bloodjournal8772649","article-title":"Site\u2010specific DNA cleavage within the MLL breakpoint cluster region induced by topoisomerase II inhibitors","volume":"87","author":"Aplan PD","year":"1996","journal-title":"Blood"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-274-8_3"},{"key":"e_1_2_4_4_1","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1182\/blood.V87.5.1912.1912","article-title":"Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment\u2010related acute myeloid leukemia: Correlation with scaffold attachment regions and topoisomerase II consensus binding sites","volume":"87","author":"Broeker PL","year":"1996","journal-title":"Blood"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.22.6611"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"e_1_2_4_7_1","first-page":"2879","article-title":"Infant acute leukemias show the same biased distribution of ALL1 gene breaks as topoisomerase II related secondary acute leukemias","volume":"57","author":"Cimino G","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_4_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6603(00)64006-0"},{"key":"e_1_2_4_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202842"},{"key":"e_1_2_4_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-115600"},{"key":"e_1_2_4_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20783"},{"key":"e_1_2_4_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2253"},{"key":"e_1_2_4_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10167"},{"key":"e_1_2_4_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-276196"},{"key":"e_1_2_4_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi002361x"},{"key":"e_1_2_4_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2007.06.009"},{"key":"e_1_2_4_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.33"},{"key":"e_1_2_4_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04740.x"},{"key":"e_1_2_4_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa042715"},{"key":"e_1_2_4_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2915"},{"key":"e_1_2_4_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011811-132434"},{"key":"e_1_2_4_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2607"},{"key":"e_1_2_4_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/372143a0"},{"key":"e_1_2_4_24_1","doi-asserted-by":"publisher","DOI":"10.3109\/07357900009038245"},{"key":"e_1_2_4_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204401"},{"key":"e_1_2_4_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/23.2.256"},{"key":"e_1_2_4_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-02-0434"},{"key":"e_1_2_4_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.070061297"},{"key":"e_1_2_4_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.10.3793"},{"key":"e_1_2_4_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401592"},{"key":"e_1_2_4_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20077"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgcc.22135","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.22135","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T04:39:26Z","timestamp":1696567166000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.22135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,5]]},"references-count":30,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,3]]}},"alternative-id":["10.1002\/gcc.22135"],"URL":"https:\/\/doi.org\/10.1002\/gcc.22135","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,5]]}}}