TY  - JOUR
AU  - Patnana, Pradeep Kumar
AU  - Liu, Longlong
AU  - Frank, Daria
AU  - Nimmagadda, Subbaiah Chary
AU  - Behrens, Matthias
AU  - Ahmed, Helal
AU  - Xie, Xiaoqing
AU  - Liebmann, Marie
AU  - Wei, Lanying
AU  - Gerdemann, Andrea
AU  - Thivakaran, Aniththa
AU  - Humpf, Hans-Ulrich
AU  - Klotz, Luisa
AU  - Dugas, Martin
AU  - Varghese, Julian
AU  - Trajkovic-Arsic, Marija
AU  - Siveke, Jens
AU  - Hanenberg, Helmut
AU  - Opalka, Bertram
AU  - Dührsen, Ulrich
AU  - Reinhardt, Hans Christian
AU  - Guenther, Ulrich
AU  - von Bubnoff, Nikolas
AU  - Khandanpour, Cyrus
TI  - Dose-dependent expression of GFI1 alters metabolism in the haematopoietic progenitors and MLL::AF9-induced leukaemic cells.
JO  - British journal of haematology
VL  - 202
IS  - 5
SN  - 0007-1048
CY  - Oxford [u.a.]
PB  - Wiley-Blackwell
M1  - DKFZ-2023-01376
SP  - 1033-1048
PY  - 2023
N1  - 2023 Sep;202(5):1033-1048
AB  - 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.
KW  - AML (Other)
KW  - GFI1 (Other)
KW  - metabolism (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37423893
DO  - DOI:10.1111/bjh.18939
UR  - https://inrepo02.dkfz.de/record/277439
ER  -