Metabolism in stem cell driven leukaemia: parallels between haematopoiesis and immunity

Rattigan, K. M., Zarou, M.-M. and Helgason, G. V. (2023) Metabolism in stem cell driven leukaemia: parallels between haematopoiesis and immunity. Blood, 141(21), pp. 2553-2565. (doi: 10.1182/blood.2022018258) (PMID:36634302) (PMCID:PMC10646800)

[img] Text
288997.pdf - Published Version
Available under License Creative Commons Attribution.



Our understanding of cancer metabolism spans from its role in cellular energetics and supplying the building blocks necessary for proliferation, to maintaining cellular redox and regulating the cellular epigenome and transcriptome. Cancer metabolism, once thought to be solely driven by upregulated glycolysis, is now known to comprise of multiple pathways with great plasticity in response to extrinsic challenges. Furthermore, cancer cells can modify their surrounding niche during disease initiation, maintenance and metastasis, contributing to therapy resistance. Leukaemia is a paradigm model of stem cell driven cancer. Here, we review how leukaemia remodels the niche and rewires its metabolism with particular attention paid to therapy-resistant stem cells. Specifically, we aim to give a global, non-exhaustive overview of key metabolic pathways. By contrasting the metabolic rewiring required by myeloid leukaemic stem cells with that required for haematopoiesis and immune cell function, we highlight the metabolic features they share. This is a critical consideration when contemplating anti-cancer metabolic inhibitor options, especially in the context of anti-cancer immune therapies. Finally, we examine pathways that have not been studied in leukaemia but are critical in solid cancers in the context of metastasis and interaction with new niches. These studies also offer detailed mechanisms that have yet to be investigated in leukaemia. Given that cancer (and normal) cells can meet their energy requirements by not only upregulating metabolic pathways, but also utilising systemically available substrates, we aim to inform how interlinked these metabolic pathways are, both within leukaemic cells and between cancer cells and their niche.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Zarou, Martha-Maria and Rattigan, Dr Kevin and Helgason, Professor Vignir
Authors: Rattigan, K. M., Zarou, M.-M., and Helgason, G. V.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Blood
Publisher:American Society of Hematology
ISSN (Online):1528-0020
Published Online:14 January 2023
Copyright Holders:Copyright © 2023 by The American Society of Hematology
First Published:First published in Blood 141(25):2553-2565
Publisher Policy:Reproduced under a Creative Commons license

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
301323Complementing LCMS data with transcriptomics to target metabolic vulnerabilities in acute myeloid leukaemiaVignir HelgasonNHS Greater Glasgow and Clyde Endowment Funds (NHSGGCEN)GN17ON425CS - Paul O'Gorman Leukaemia Research Centre
303409Targeting mitochondrial fuel oxidation for the treatment of chronic and acute myeloid leukaemiasVignir HelgasonBloodwise (BLOODWIS)18006CS - Paul O'Gorman Leukaemia Research Centre
174115CRUK Centre RenewalOwen SansomCancer Research UK (CRUK)C7932/A25142CS - Beatson Institute for Cancer Research
307077Targeting Autophagy and Aberrant Metabolism of Leukaemic Stem CellsVignir HelgasonCancer Research UK (CRUK)C57352/A29754CS -Translational Research Centre