- LSF ID
- 59282
- ORCID
- 0000-0002-8772-4778
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
- LSF ID
- 14567
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
- GND
- 1073185001
- LSF ID
- 14454
- ORCID
- 0000-0002-4034-9472
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
- LSF ID
- 61540
- ORCID
- 0000-0001-5706-9349
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
- GND
- 130838004
- LSF ID
- 12956
- ORCID
- 0000-0003-4655-6269
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
korrespondierende*r Autor*in
Abstract in Englisch:
Growth factor independence 1 (GFI1) is a transcriptional repressor protein that plays an essential role in the differentiation of myeloid and lymphoid progenitors. We and other groups have shown that GFI1 has a dose-dependent role in the initiation, progression, and prognosis of acute myeloid leukaemia (AML) patients by inducing epigenetic changes. We now demonstrate a novel role for dose-dependent GFI1 expression in regulating metabolism in haematopoietic progenitor and leukaemic cells. Using in-vitro and ex-vivo murine models of MLL::AF9-induced human AML and extra-cellular flux assays, we now demonstrate that a lower GFI1 expression enhances oxidative phosphorylation rate via upregulation of the FOXO1- MYC axis. Our findings underscore the significance of therapeutic exploitation in GFI1-low-expressing leukaemia cells by targeting oxidative phosphorylation and glutamine metabolism.