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In embryonic and pluripotent stem cells, it maintains self\u2010renewal by silencing endogenous retroelements through the establishment of heterochromatin. While these canonical functions have been extensively examined in embryonic stem (ES) cells, accumulating evidence also highlights its diverse contributions to cancer biology. We herein focused on the oncogenic role of TIF1\u03b2 in leukemic progression, contrasting this with its physiological roles in hematopoietic stem cell maintenance, differentiation, and immune regulation, thereby providing a comparative perspective on H3K9 methyltransferase SETDB1\u2010dependent and \u2010independent mechanisms. TIF1\u03b2\u2010mediated epigenetic plasticity was recently shown to establish a leukemic chromatin environment for promoting oncogenic transcriptional programs while repressing lineage\u2010differentiation regulators, which drives leukemic progression in a context\u2010dependent manner. This review summarizes the dual role of TIF1\u03b2 as a chromatin modulator, functioning both as a canonical transcriptional co\u2010repressor and as a context\u2010dependent co\u2010activator, and also discusses how these modalities cooperate to sustain leukemic stem cell programs.<\/jats:p>","DOI":"10.1111\/cas.70334","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T07:23:07Z","timestamp":1769584987000},"page":"896-903","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Roles of\n                    <scp>TIF1\u03b2<\/scp>\n                    in Leukemic Stem Cell Through\n                    <scp>SETDB1<\/scp>\n                    \u2010Dependent and Independent Mechanisms"],"prefix":"10.1111","volume":"117","author":[{"given":"Mariko","family":"Morii","sequence":"first","affiliation":[{"name":"Graduate School of Interdisciplinary Science and Engineering in Health Systems 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