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Autophagy and mitochondrial metabolism: insights into their role and therapeutic potential in chronic myeloid leukaemia
Author(s) -
Baquero Pablo,
Dawson Amy,
Helgason Gudmundur Vignir
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14659
Subject(s) - autophagy , chronic myeloid leukaemia , biology , tyrosine kinase , cancer research , mechanism (biology) , mitochondrion , stem cell , myeloid , immunology , microbiology and biotechnology , apoptosis , signal transduction , genetics , philosophy , epistemology
Despite the development of selective BCR ‐ ABL ‐targeting tyrosine kinase inhibitors ( TKI s) transforming the management of chronic myeloid leukaemia ( CML ), therapy‐resistant leukaemic stem cells ( LSC s) 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 LSC s to work towards the goal of eradicating LSC s 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 LSC s 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).