Abstract
TG‐Interacting Factor 1 (Tgif1) affects proliferation and differentiation of myeloid cells and regulates self‐renewal of haematopoietic stem cells (HSCs). To determine its impact on leukaemic haematopoiesis, we induced acute or chronic myeloid leukaemias (AML or CML) in mice by enforced expression of MLL‐AF9 or BCR‐ABL, respectively, in Tgif1+/+ or Tgif1−/− haematopoietic stem and progenitor cells (HSPCs) and transplanted them into syngeneic recipients. We find that loss of Tgif1 accelerates leukaemic progression and shortens survival in mice with either AML or CML. Leukaemia‐initiating cells (LICs) occur with higher frequency in AML among mice transplanted with MLL‐AF9‐transduced Tgif1−/− HSPCs than with Tgif1+/+ BMCs. Moreover, AML in mice generated with Tgif1−/− HSPCs are chemotherapy resistant and relapse more rapidly than those whose AML arose in Tgif1+/+ HSPCs. Whole transcriptome analysis shows significant alterations in gene expression profiles associated with transforming growth factor‐beta (TGF‐beta) and retinoic acid (RA) signalling pathways because of Tgif1 loss. These findings indicate that Tgif1 has a protective role in myeloid leukaemia initiation and progression, and its anti‐leukaemic contributions are connected to TGF‐beta‐ and RA‐driven functions.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.