Autophagy and mitochondrial metabolism: insights into the role and therapeutic potential in chronic myeloid leukaemia

Baquero, P., Dawson, A. and Helgason, G. V. (2019) Autophagy and mitochondrial metabolism: insights into the role and therapeutic potential in chronic myeloid leukaemia. FEBS Journal, 286(7), pp. 1271-1283. (doi:10.1111/febs.14659) (PMID:30222247)

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Abstract

Despite the development of selective BCR‐ABL‐targeting tyrosine kinase inhibitors (TKIs) transforming the management of chronic myeloid leukaemia (CML), therapy‐resistant leukaemic stem cells (LSCs) persist after TKI treatment and present an obstacle to a CML cure. Recently, we and others have made significant contributions to the field by unravelling survival dependencies in LSCs to work towards the goal of eradicating LSCs in CML patients. In this review, we describe these findings focusing on autophagy and mitochondrial metabolism, which have recently been uncovered as two essential processes for LSCs quiescence and survival, respectively. In addition, we discuss the therapeutic potential of autophagy and mitochondrial metabolism inhibition as a strategy to eliminate CML cells in patients where the resistance to TKI is driven by BCR‐ABL‐independent mechanism(s).

Item Type:Articles
Additional Information:Also funded by Leuka; the Howat Foundation, Lady Tata Memorial Trust and Friends of Paul O'Gorman Leukaemia Research Centre.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Helgason, Dr Vignir and Dawson, Amy and Baquero, Dr Pablo
Authors: Baquero, P., Dawson, A., and Helgason, G. V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:FEBS Journal
Publisher:Wiley
ISSN:1742-464X
ISSN (Online):1742-4658
Published Online:17 September 2018
Copyright Holders:Copyright © 2018 Federation of European Biochemical Societies
First Published:First published in FEBS Journal 286(7): 1271-1283
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
722281Identifying and Targeting Metabolic Dependencies in Tyrosine Kinase-Driven Myeloid LeukaemiasVignir HelgasonThe Kay Kendall Leukaemia Fund (KENDALL)KKL1069RI CANCER SCIENCES