TY - JOUR
T1 - Dose-dependent expression of GFI1 alters metabolism in the haematopoietic progenitors and MLL::AF9-induced leukaemic cells
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 T.
AU - Hanenberg, Helmut
AU - Opalka, Bertram
AU - Dührsen, Ulrich
AU - Reinhardt, Hans Christian
AU - Guenther, Ulrich
AU - von Bubnoff, Nikolas
AU - Khandanpour, Cyrus
N1 - Publisher Copyright:
© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
PY - 2023/9
Y1 - 2023/9
N2 - 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.
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
KW - GFI1
KW - metabolism
UR - http://www.scopus.com/inward/record.url?scp=85164570701&partnerID=8YFLogxK
U2 - 10.1111/bjh.18939
DO - 10.1111/bjh.18939
M3 - Article
C2 - 37423893
AN - SCOPUS:85164570701
SN - 0007-1048
VL - 202
SP - 1033
EP - 1048
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 5
ER -