Journal Article

DKFZ-2023-01376

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dose-dependent expression of GFI1 alters metabolism in the haematopoietic progenitors and MLL::AF9-induced leukaemic cells.

Patnana, P. K. ; Liu, L. ; Frank, D. ; Nimmagadda, S. C. ; Behrens, M. ; Ahmed, H. ; Xie, X. ; Liebmann, M. ; Wei, L. ; Gerdemann, A. ; Thivakaran, A. ; Humpf, H.-U. ; Klotz, L. ; Dugas, M. ; Varghese, J. ; Trajkovic-Arsic, M.DKFZ* ; Siveke, J.DKFZ* ; Hanenberg, H. ; Opalka, B. ; Dührsen, U. ; Reinhardt, H. C. ; Guenther, U. ; von Bubnoff, N. ; Khandanpour, C.

2023
Wiley-Blackwell Oxford [u.a.]

This record in other databases:  

Please use a persistent id in citations: doi:10.1111/bjh.18939

Abstract: 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.

Keyword(s): AML ; GFI1 ; metabolism

Note: 2023 Sep;202(5):1033-1048

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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