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Here, we demonstrated that plant homeodomain finger protein 8 (PHF8), a histone demethylase was aberrantly enriched in CML samples compared to healthy controls. PHF8 inhibited CML cell differentiation and promoted CML cell proliferation. Furthermore, the proliferation\u2010inhibited function of PHF8\u2010knockdown have stronger effect on imatinib mesylate (IM)\u2010resistant CML cells. Mechanistically, we identified that PHF8 as a transcriptional modulator interacted with the promoter of the <jats:italic>BCR<\/jats:italic>::<jats:italic>ABL1<\/jats:italic> fusion gene and alters the methylation levels of H3K9me1, H3K9me2 and H3K27me1, thereby promoting <jats:italic>BCR<\/jats:italic>::<jats:italic>ABL1<\/jats:italic> transcription. Overall, our study suggests that targeting PHF8, which directly regulates <jats:italic>BCR<\/jats:italic>::<jats:italic>ABL1<\/jats:italic> expression, is a useful therapeutic approach for CML.<\/jats:p>","DOI":"10.1111\/bjh.18983","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T05:09:49Z","timestamp":1689829789000},"page":"1178-1191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Histone demethylase <scp>PHF8<\/scp> facilitates the development of chronic myeloid leukaemia by directly targeting <i>BCR::ABL1<\/i>"],"prefix":"10.1111","volume":"202","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7246-7975","authenticated-orcid":false,"given":"Huimin","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Hematology, Qilu Hospital of Shandong University, Cheeloo College of Medicine Shandong University  Jinan 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