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We found that IFN-\u03b1 upregulated CCAAT\/enhancer binding protein \u03b2 (C\/EBP\u03b2) in BCR-ABL\u2013expressing mouse cells by activating STAT1 and STAT5, which were recruited to a newly identified 3\u2032 distal enhancer of Cebpb that contains tandemly aligned IFN-\u03b3\u2013activated site elements. Suppression or deletion of the IFN-\u03b3\u2013activated site elements abrogated IFN-\u03b1\u2013dependent upregulation of C\/EBP\u03b2. IFN-\u03b1 induced differentiation and exhaustion of CML stem cells, both in vitro and in vivo, in a C\/EBP\u03b2-dependent manner. In addition, IFN-\u03b1 upregulated C\/EBP\u03b2 and induced exhaustion of lineage\u2212 CD34+ cells from CML patients. Collectively, these results clearly indicate that C\/EBP\u03b2 is a critical mediator of IFN-\u03b1\u2013induced differentiation and exhaustion of CML stem cells.<\/jats:p>","DOI":"10.1182\/bloodadvances.2018020503","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T16:45:21Z","timestamp":1549989921000},"page":"476-488","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":23,"title":["C\/EBP\u03b2 is a critical mediator of IFN-\u03b1\u2013induced exhaustion of chronic myeloid leukemia stem cells"],"prefix":"10.1182","volume":"3","author":[{"given":"Asumi","family":"Yokota","sequence":"first","affiliation":[{"name":"Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan;"},{"name":"Division of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9036-4865","authenticated-orcid":false,"given":"Hideyo","family":"Hirai","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuichi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiko","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1490-9923","authenticated-orcid":false,"given":"Yoshihiro","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Division of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH;"},{"name":"Laboratory of Oncology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoka","family":"Kamio","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G","family":". 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