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To determine its impact on leukaemic haematopoiesis, we induced acute or chronic myeloid leukaemias (AML or CML) in mice by enforced expression of <jats:italic>MLL\u2010AF9<\/jats:italic> or <jats:italic>BCR\u2010ABL<\/jats:italic>, respectively, in <jats:italic>Tgif1<jats:sup>+\/+<\/jats:sup><\/jats:italic> or <jats:italic>Tgif1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> haematopoietic stem and progenitor cells (HSPCs) and transplanted them into syngeneic recipients. We find that loss of <jats:italic>Tgif1<\/jats:italic> accelerates leukaemic progression and shortens survival in mice with either AML or CML. Leukaemia\u2010initiating cells (LICs) occur with higher frequency in AML among mice transplanted with <jats:italic>MLL\u2010AF9<\/jats:italic>\u2010transduced <jats:italic>Tgif1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> HSPCs than with <jats:italic>Tgif1<jats:sup>+\/+<\/jats:sup><\/jats:italic> BMCs. Moreover, AML in mice generated with <jats:italic>Tgif1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> HSPCs are chemotherapy resistant and relapse more rapidly than those whose AML arose in <jats:italic>Tgif1<jats:sup>+\/+<\/jats:sup><\/jats:italic> HSPCs. Whole transcriptome analysis shows significant alterations in gene expression profiles associated with transforming growth factor\u2010beta (TGF\u2010beta) and retinoic acid (RA) signalling pathways because of <jats:italic>Tgif1<\/jats:italic> loss. These findings indicate that <jats:italic>Tgif1<\/jats:italic> has a protective role in myeloid leukaemia initiation and progression, and its anti\u2010leukaemic contributions are connected to TGF\u2010beta\u2010 and RA\u2010driven functions.<\/jats:p>","DOI":"10.1111\/jcmm.15977","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T13:20:50Z","timestamp":1602768050000},"page":"13472-13480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Loss of <i>TG\u2010Interacting Factor 1<\/i> decreases survival in mouse models of myeloid leukaemia"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5727-3278","authenticated-orcid":false,"given":"Ling","family":"Yan","sequence":"first","affiliation":[{"name":"Departments of Pediatrics Vanderbilt University Medical Center  Nashville TN 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