{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:22:22Z","timestamp":1790306542712,"version":"4.1.0"},"reference-count":47,"publisher":"American Society of Hematology","issue":"21","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,11,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inversion of chromosome 16 is a consistent finding in patients with acute myeloid leukemia subtype M4 with eosinophilia, which generates a CBFB-MYH11 fusion gene. It is generally considered that CBF\u03b2-SMMHC, the fusion protein encoded by CBFB-MYH11, is a dominant negative repressor of RUNX1. However, recent findings challenge the RUNX1-repression model for CBF\u03b2-SMMHC\u2013mediated leukemogenesis. To definitively address the role of Runx1 in CBFB-MYH11\u2013induced leukemia, we crossed conditional Runx1 knockout mice (Runx1f\/f) with conditional Cbfb-MYH11 knockin mice (Cbfb+\/56M). On Mx1-Cre activation in hematopoietic cells induced by poly (I:C) injection, all Mx1-CreCbfb+\/56M mice developed leukemia in 5 months, whereas no leukemia developed in Runx1f\/fMx1-CreCbfb+\/56M mice, and this effect was cell autonomous. Importantly, the abnormal myeloid progenitors (AMPs), a leukemia-initiating cell population induced by Cbfb-MYH11 in the bone marrow, decreased and disappeared in Runx1f\/fMx1-CreCbfb+\/56M mice. RNA-seq analysis of AMP cells showed that genes associated with proliferation, differentiation blockage, and leukemia initiation were differentially expressed between Mx1-CreCbfb+\/56M and Runx1f\/fMx1-CreCbfb+\/56M mice. In addition, with the chromatin immunocleavage sequencing assay, we observed a significant enrichment of RUNX1\/CBF\u03b2-SMMHC target genes in Runx1f\/fMx1-CreCbfb+\/56M cells, especially among downregulated genes, suggesting that RUNX1 and CBF\u03b2-SMMHC mainly function together as activators of gene expression through direct target gene binding. These data indicate that Runx1 is indispensable for Cbfb-MYH11\u2013induced leukemogenesis by working together with CBF\u03b2-SMMHC to regulate critical genes associated with the generation of a functional AMP population.<\/jats:p>","DOI":"10.1182\/blood.2020007747","type":"journal-article","created":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T22:48:27Z","timestamp":1600123707000},"page":"2373-2385","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":41,"title":["RUNX1 and CBF\u03b2-SMMHC transactivate target genes together in abnormal myeloid progenitors for leukemia development"],"prefix":"10.1182","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5214-7870","authenticated-orcid":false,"given":"Tao","family":"Zhen","sequence":"first","affiliation":[{"name":"Oncogenesis and Development Section, National Human Genome Research Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4665-1517","authenticated-orcid":false,"given":"Yaqiang","family":"Cao","sequence":"additional","affiliation":[{"name":"Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9690-5995","authenticated-orcid":false,"given":"Gang","family":"Ren","sequence":"additional","affiliation":[{"name":"Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9799-5830","authenticated-orcid":false,"given":"Ling","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2808-1749","authenticated-orcid":false,"given":"R. 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