{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:53:50Z","timestamp":1792194830011,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,11,2]],"date-time":"2018-11-02T00:00:00Z","timestamp":1541116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA100159R15GM120715"],"award-info":[{"award-number":["R01CA100159R15GM120715"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p>Infant acute leukemias are aggressive and characterized by rapid onset after birth. The majority harbor translocations involving the <jats:italic>MLL<\/jats:italic> gene with <jats:italic>AF9<\/jats:italic> as one of its most common fusion partners. <jats:italic>MLL<\/jats:italic> and <jats:italic>AF9<\/jats:italic> loci contain breakpoint cluster regions (bcrs) with sequences hypothesized to be targets of topoisomerase II inhibitors that promote translocation formation. Overlap of <jats:italic>MLL<\/jats:italic> bcr sequences associated with both infant acute leukemia and therapy\u2010related 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. We established a reporter system to systematically quantitate and stratify the potential for such compounds to promote chromosomal translocations between the <jats:italic>MLL<\/jats:italic> and <jats:italic>AF9<\/jats:italic> bcrs analogous to those in infant leukemia. We show bioflavonoids genistein and quercetin most biochemically similar to etoposide have a strong association with <jats:italic>MLL\u2010AF9<\/jats:italic> 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. The frequency of translocations induced by bioflavonoids at later stages of myelopoiesis is significantly reduced by more than one log. The <jats:italic>MLL<\/jats:italic> and <jats:italic>AF9<\/jats:italic> bcrs are sensitive to these agents and recombinogenic independent of their native context suggesting bcr sequences themselves are drivers of illegitimate DNA repair reactions and translocations, not generation of functional oncogenic fusions. This system provides for rapid systematic screening of relative risk, dose dependence, and combinatorial impact of multitudes of dietary and environmental exposures on <jats:italic>MLL\u2010AF9<\/jats:italic> translocations. Environ. Mol. Mutagen. 60: 154\u2013167, 2019. \u00a9 2018 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/em.22245","type":"journal-article","created":{"date-parts":[[2018,11,2]],"date-time":"2018-11-02T11:00:41Z","timestamp":1541156441000},"page":"154-167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Bioflavonoids promote stable translocations between <i>MLL<\/i>\u2010<i>AF9<\/i> breakpoint cluster regions independent of normal chromosomal context: Model system to screen environmental risks"],"prefix":"10.1002","volume":"60","author":[{"given":"Bhawana","family":"Bariar","sequence":"first","affiliation":[{"name":"Department of Biological Sciences University of North Carolina at Charlotte  9201 University City Boulevard, Charlotte North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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