{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T18:06:22Z","timestamp":1779213982255,"version":"3.51.4"},"reference-count":72,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":57,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NHGRI, NIH","award":["1ZIAHG000030"],"award-info":[{"award-number":["1ZIAHG000030"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:p>\n                    The leukemia fusion gene\n                    <jats:italic>CBFB-MYH11<\/jats:italic>\n                    requires RUNX1 for leukemogenesis, but the underlying mechanism is unclear. By in vitro studies, we found that CBF\u03b2-SMMHC, the chimeric protein encoded by\n                    <jats:italic>CBFB-MYH11<\/jats:italic>\n                    , could enhance the binding affinity between RUNX1 and its target DNA. Increased RUNX1-DNA binding was also observed in myeloid progenitor cells from mice expressing CBF\u03b2-SMMHC. Moreover, only CBF\u03b2-SMMHC variants able to enhance the DNA binding affinity by RUNX1 could induce leukemia in mouse models. Marked transcriptomic changes, affecting genes associated with inflammatory response and target genes of CBFA2T3, were observed in mice expressing leukemogenic CBF\u03b2-SMMHC variants. Finally, we show that CBF\u03b2-SMMHC could not induce leukemia in mice with a\n                    <jats:italic>Runx1<\/jats:italic>\n                    -R188Q mutation, which reduces RUNX1 DNA binding but does not affect its interaction with CBF\u03b2-SMMHC or its sequestration to cytoplasm by CBF\u03b2-SMMHC. Our data suggest that, in addition to binding RUNX1 to regulate gene expression, enhancing RUNX1 binding affinity to its target DNA is an important mechanism by which CBF\u03b2-SMMHC contributes to leukemogenesis, highlighting RUNX1-DNA interaction as a potential therapeutic target in inv(16) acute myeloid leukemia.\n                  <\/jats:p>","DOI":"10.1172\/jci192923","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T19:46:41Z","timestamp":1754423201000},"source":"Crossref","is-referenced-by-count":2,"title":["CBF\u03b2-SMMHC\u2013driven leukemogenesis requires enhanced RUNX1-DNA binding affinity in mice"],"prefix":"10.1172","volume":"135","author":[{"given":"Tao","family":"Zhen","sequence":"first","affiliation":[{"name":"Oncogenesis and Development Section, Translational and Functional Genomics Branch, National Human Genome Research Institute (NHGRI), NIH, Bethesda, Maryland, 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