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)

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, Professor 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 > School 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
171051		Targeting p53, cMyc and PRC2 regulatory hubs: A systematic and stratified approach to deliver new therapeutics for CML	David Vetrie	Bloodwise (BLOODWIS)	14033	CS - Paul O'Gorman Leukaemia Research Centre
301129		TASTER (TArgeting STEm cell Resistance) - Defining leukaemic cell clonal architecture to inform and monitor drug responses in the TASTER CML Phase II Clinical Trial	Mhairi Copland	Cancer Research UK (CRUK)	C55731/A24896	CS - Paul O'Gorman Leukaemia Research Centre
173136		Identifying and Targeting Metabolic Dependencies in Tyrosine Kinase-Driven Myeloid Leukaemias	Vignir Helgason	The Kay Kendall Leukaemia Fund (KENDALL)	KKL1069	CS - Paul O'Gorman Leukaemia Research Centre
303409		Targeting mitochondrial fuel oxidation for the treatment of chronic and acute myeloid leukaemias	Vignir Helgason	Bloodwise (BLOODWIS)	18006	CS - Paul O'Gorman Leukaemia Research Centre