{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T02:55:00Z","timestamp":1773802500158,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,8,11]],"date-time":"2004-08-11T00:00:00Z","timestamp":1092182400000},"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":[[2004,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The recurring chromosome translocation t(11;16)(q23;p13) is detected in leukemia patients, virtually all of whom have received previous chemotherapy with topoisomerase (topo) II inhibitors. In the t(11;16), 3\u2032 <jats:italic>CBP<\/jats:italic>, on 16p13, is fused to 5\u2032 <jats:italic>MLL<\/jats:italic>, on 11q23, resulting in an <jats:italic>MLL<\/jats:italic>\u2013<jats:italic>CBP<\/jats:italic> fusion gene that plays an important role in leukemogenesis. In this study, we cloned genomic breakpoints of the <jats:italic>MLL<\/jats:italic> and <jats:italic>CBP<\/jats:italic> genes in the t(11;16) in the SN\u20101 cell line and in five patients with therapy\u2010related leukemia, all of whom had received topo II inhibitors for previous tumors. In all patients except one, both the genomic <jats:italic>MLL<\/jats:italic>\u2013<jats:italic>CBP<\/jats:italic> and the reciprocal fusions were cloned. Genomic breakpoints in <jats:italic>MLL<\/jats:italic> occurred in the 8.3\u2010kb breakpoint cluster region in all patients, whereas the breakpoints in <jats:italic>CBP<\/jats:italic> clustered in an 8.2\u2010kb region of intron 3 in four patients. Genomic breakpoints in <jats:italic>MLL<\/jats:italic> occurred in intron 11 near the topo II cleavage site in the SN\u20101 cell line and in one patient, and they were close to LINE repetitive sequences in two other patients. In the remaining two patients, genomic breakpoints were in intron 9 in Alu repeats. Genomic breakpoints in <jats:italic>CBP<\/jats:italic> occurred in and around Alu repeats in one and two patients, respectively. In two patients, the breaks were near LINE repetitive sequences, suggesting that repetitive DNA sequences may play a role. No specific recombination motifs were identified at or near the breakpoint junctions. No topo II cleavage sites were detected in introns 2 and 3 of <jats:italic>CBP<\/jats:italic>. However, there were deletions and duplications at the breakpoints in both <jats:italic>MLL<\/jats:italic> and <jats:italic>CBP<\/jats:italic> and microhomologies or nontemplated nucleotides at most of the genomic fusion junctions, suggesting that a nonhomologous end\u2010joining repair mechanism was involved in the t(11;16). \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20077","type":"journal-article","created":{"date-parts":[[2004,8,11]],"date-time":"2004-08-11T18:14:21Z","timestamp":1092248061000},"page":"257-265","source":"Crossref","is-referenced-by-count":26,"title":["Characterization of genomic breakpoints in <i>MLL<\/i> and <i>CBP<\/i> in leukemia patients with t(11;16)"],"prefix":"10.1002","volume":"41","author":[{"given":"Yanming","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Zeleznik\u2010Le","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neelmini","family":"Emmanuel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nimanthi","family":"Jayathilaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela","family":"Strissel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reiner","family":"Strick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loretta","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Beth","family":"Neilly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiko","family":"Taki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhide","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiko","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitte","family":"Schlegelberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet D.","family":"Rowley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,8,11]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0695-167"},{"key":"e_1_2_5_3_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_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401223"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0996-33"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.19.7631"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.171.2.489"},{"key":"e_1_2_5_8_1","first-page":"1305","article-title":"Molecular analysis of 13 cases of MLL\/11q23 secondary acute leukemia and identification of topo II consensus\u2010binding 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_5_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.11.3250.bloodjournal85113250"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202842"},{"key":"e_1_2_5_11_1","first-page":"185","article-title":"Identification of complex genomic breakpoint junction in the t(9;11) MLL\u2010AF9 fusion gene in acute leukemia","volume":"10","author":"Gill\u2010Super H","year":"1997","journal-title":"Genes Chromosomes Cancer"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1259"},{"key":"e_1_2_5_13_1","first-page":"1139","article-title":"SN\u20101, a novel leukemic cell line with t(11;16)(q23;p13): myeloid characteristic and resistance to retinoids and vitamin D3","volume":"60","author":"Hayashi Y","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_5_14_1","unstructured":"HuretJL SenonS.2003. 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