%0 Journal Article
%A Patnana, Pradeep Kumar
%A Liu, Longlong
%A Frank, Daria
%A Nimmagadda, Subbaiah Chary
%A Behrens, Matthias
%A Ahmed, Helal
%A Xie, Xiaoqing
%A Liebmann, Marie
%A Wei, Lanying
%A Gerdemann, Andrea
%A Thivakaran, Aniththa
%A Humpf, Hans-Ulrich
%A Klotz, Luisa
%A Dugas, Martin
%A Varghese, Julian
%A Trajkovic-Arsic, Marija
%A Siveke, Jens
%A Hanenberg, Helmut
%A Opalka, Bertram
%A Dührsen, Ulrich
%A Reinhardt, Hans Christian
%A Guenther, Ulrich
%A von Bubnoff, Nikolas
%A Khandanpour, Cyrus
%T Dose-dependent expression of GFI1 alters metabolism in the haematopoietic progenitors and MLL::AF9-induced leukaemic cells.
%J British journal of haematology
%V 202
%N 5
%@ 0007-1048
%C Oxford [u.a.]
%I Wiley-Blackwell
%M DKFZ-2023-01376
%P 1033-1048
%D 2023
%Z 2023 Sep;202(5):1033-1048
%X 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.
%K AML (Other)
%K GFI1 (Other)
%K metabolism (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37423893
%R 10.1111/bjh.18939
%U https://inrepo02.dkfz.de/record/277439