The leukaemia stem cell: similarities, differences and clinical prospects in CML and AML

Vetrie, D. , Helgason, V. and Copland, M. (2020) The leukaemia stem cell: similarities, differences and clinical prospects in CML and AML. Nature Reviews Cancer, 20, pp. 158-173. (doi: 10.1038/s41568-019-0230-9) (PMID:31907378)

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Abstract

For two decades, leukaemia stem cells (LSCs) in chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) have been advanced paradigms for the cancer stem cell field. In CML, the acquisition of the fusion tyrosine kinase BCR–ABL1 in a haematopoietic stem cell drives its transformation to become a LSC. In AML, LSCs can arise from multiple cell types through the activity of a number of oncogenic drivers and pre-leukaemic events, adding further layers of context and genetic and cellular heterogeneity to AML LSCs not observed in most cases of CML. Furthermore, LSCs from both AML and CML can be refractory to standard-of-care therapies and persist in patients, diversify clonally and serve as reservoirs to drive relapse, recurrence or progression to more aggressive forms. Despite these complexities, LSCs in both diseases share biological features, making them distinct from other CML or AML progenitor cells and from normal haematopoietic stem cells. These features may represent Achilles’ heels against which novel therapies can be developed. Here, we review many of the similarities and differences that exist between LSCs in CML and AML and examine the therapeutic strategies that could be used to eradicate them.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Helgason, Dr Vignir and Vetrie, Professor David and Copland, Professor Mhairi
Authors: Vetrie, D., Helgason, V., and Copland, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Nature Reviews Cancer
Publisher:Nature Research
ISSN:1474-175X
ISSN (Online):1474-1768
Published Online:06 January 2020
Copyright Holders:Copyright © Springer Nature Limited 2020
First Published:First published in Nature Reviews Cancer 20:158-173
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
171051Targeting p53, cMyc and PRC2 regulatory hubs: A systematic and stratified approach to deliver new therapeutics for CMLDavid VetrieBloodwise (BLOODWIS)14033CS - Paul O'Gorman Leukaemia Research Centre
301129TASTER (TArgeting STEm cell Resistance) - Defining leukaemic cell clonal architecture to inform and monitor drug responses in the TASTER CML Phase II Clinical TrialMhairi CoplandCancer Research UK (CRUK)C55731/A24896CS - Paul O'Gorman Leukaemia Research Centre
173136Identifying and Targeting Metabolic Dependencies in Tyrosine Kinase-Driven Myeloid LeukaemiasVignir HelgasonThe Kay Kendall Leukaemia Fund (KENDALL)KKL1069CS - 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