Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia

de Beauchamp, L., Himonas, E. and Helgason, G. V. (2022) Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia. Leukemia, 36(1), pp. 1-12. (doi: 10.1038/s41375-021-01416-w) (PMID:34561557) (PMCID:PMC8727299)

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While the understanding of the genomic aberrations that underpin chronic and acute myeloid leukaemia (CML and AML) has allowed the development of therapies for these diseases, limitations remain. These become apparent when looking at the frequency of treatment resistance leading to disease relapse in leukaemia patients. Key questions regarding the fundamental biology of the leukaemic cells, such as their metabolic dependencies, are still unresolved. Even though a majority of leukaemic cells are killed during initial treatment, persistent leukaemic stem cells (LSCs) and therapy-resistant cells are still not eradicated with current treatments, due to various mechanisms that may contribute to therapy resistance, including cellular metabolic adaptations. In fact, recent studies have shown that LSCs and treatment-resistant cells are dependent on mitochondrial metabolism, hence rendering them sensitive to inhibition of mitochondrial oxidative phosphorylation (OXPHOS). As a result, rewired energy metabolism in leukaemic cells is now considered an attractive therapeutic target and the significance of this process is increasingly being recognised in various haematological malignancies. Therefore, identifying and targeting aberrant metabolism in drug-resistant leukaemic cells is an imperative and a relevant strategy for the development of new therapeutic options in leukaemia. In this review, we present a detailed overview of the most recent studies that present experimental evidence on how leukaemic cells can metabolically rewire, more specifically the importance of OXPHOS in LSCs and treatment-resistant cells, and the current drugs available to target this process. We highlight that uncovering specific energy metabolism dependencies will guide the identification of new and more targeted therapeutic strategies for myeloid leukaemia.

Item Type:Articles
Additional Information:The work was supported by University of Glasgow MVLS DTP Studentship, MRC confidence in Concept 2018 (MC_PC_18048), The Howat Foundation and Cancer Research UK (C57352/A29754).
Glasgow Author(s) Enlighten ID:Helgason, Professor Vignir
Authors: de Beauchamp, L., Himonas, E., and Helgason, G. V.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Leukemia
Publisher:Springer Nature
ISSN (Online):1476-5551
Published Online:24 September 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Leukemia 36(1): 1-12
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
306054Confidence in Concept 2019Anna DominiczakMedical Research Council (MRC)MC_PC_18048MVLS - College Senior Management
307077Targeting Autophagy and Aberrant Metabolism of Leukaemic Stem CellsVignir HelgasonCancer Research UK (CRUK)C57352/A29754CS -Translational Research Centre