{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T23:40:33Z","timestamp":1695512433718},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,7,30]],"date-time":"2012-07-30T00:00:00Z","timestamp":1343606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:italic><jats:styled-content style=\"fixed-case\">MLL<\/jats:styled-content><\/jats:italic> rearrangements were analysed in the blood of a patient receiving chemotherapy for diffuse large B\u2010cell lymphoma using inverse polymerase chain reaction targeting exon 12, parallel sequencing and a custom algorithm design. Of thirteen <jats:italic><jats:styled-content style=\"fixed-case\">MLL<\/jats:styled-content><\/jats:italic> rearrangements detected, five were capable of generating <jats:italic><jats:styled-content style=\"fixed-case\">MLL<\/jats:styled-content><\/jats:italic> fusion genes, including <jats:italic><jats:styled-content style=\"fixed-case\">MLL<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MLLT<\/jats:styled-content>3<\/jats:italic>, the most common fusion in acute myeloid leukaemia (<jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content>). Other fusions, all previously clinically unobserved, included <jats:italic><jats:styled-content style=\"fixed-case\">MLL<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">NKD<\/jats:styled-content>1<\/jats:italic>, a fusion to the negative regulator of <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>nt\/\u03b2\u2010catenin signaling, a pathway linked to leukaemic cell proliferation. The majority of the fusions exhibited clonal persistence from before treatment until 6\u00a0months post\u2010chemotherapy, suggesting the fusions may confer a survival advantage to the mutant clone. <jats:italic><jats:styled-content style=\"fixed-case\">MLL<\/jats:styled-content><\/jats:italic> breakpoints were partly clustered at a specific location, indicating commonality in the process of their formation. Further, the same <jats:italic><jats:styled-content style=\"fixed-case\">MLL<\/jats:styled-content><\/jats:italic> breakpoint location exhibited a 50\u2013100\u2010fold increase in <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content> to <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> transitions, consistent with attack by activation\u2010induced cytidine deaminase (<jats:italic><jats:styled-content style=\"fixed-case\">AICDA<\/jats:styled-content><\/jats:italic>). As is also observed in <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content> and acute lymphoblastic leukaemia, in this single patient setting, <jats:italic><jats:styled-content style=\"fixed-case\">MLL<\/jats:styled-content><\/jats:italic> is capable of interacting with multiple fusion partners. This finding defines a discrete site of <jats:italic><jats:styled-content style=\"fixed-case\">MLL<\/jats:styled-content><\/jats:italic> susceptibility to fragmentation, linked to possible deregulation of <jats:italic><jats:styled-content style=\"fixed-case\">AICDA<\/jats:styled-content><\/jats:italic> function.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2012.09248.x","type":"journal-article","created":{"date-parts":[[2012,7,30]],"date-time":"2012-07-30T07:18:25Z","timestamp":1343632705000},"page":"50-57","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Multiple clonal <i><scp>MLL<\/scp><\/i> fusions in a patient receiving <scp>CHOP<\/scp>\u2010based chemotherapy"],"prefix":"10.1111","volume":"159","author":[{"given":"Shyh\u2010Jen","family":"Shih","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology University of California Davis Sacramento CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Fass","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Genome Center University of California Davis Sacramento CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Buffalo","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Genome Center University of California Davis Sacramento CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawei","family":"Lin","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Genome Center University of California Davis Sacramento CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheetal P.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of California Davis Sacramento CA USA"},{"name":"Research Services VA Northern California Health Care System Mather CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel O.","family":"Diaz","sequence":"additional","affiliation":[{"name":"Department of Medicine Loyola University Medical Center Maywood IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew T.","family":"Vaughan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of California Davis Sacramento CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,7,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1111603"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1139851"},{"key":"e_1_2_8_4_1","first-page":"4550","article-title":"Apoptotic triggers initiate translocations within the MLL gene involving the nonhomologous end joining repair system","volume":"61","author":"Betti C.J.","year":"2001","journal-title":"Cancer Research"},{"key":"e_1_2_8_5_1","first-page":"1377","article-title":"Apoptotic stimuli initiate MLL\u2010AF9 translocations that are transcribed in cells capable of division","volume":"63","author":"Betti C.J.","year":"2003","journal-title":"Cancer Research"},{"key":"e_1_2_8_6_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 P.L.","year":"1996","journal-title":"Blood"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"5844","DOI":"10.1074\/jbc.271.10.5844","article-title":"A novel function for the second C2 domain of synaptotagmin. 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