Abstract
The insensitivity of Chronic Myeloid Leukaemia (CML) stem cells to Tyrosine Kinase Inhibitor (TKI) treatment is now believed to be the main reason for disease persistence experienced in patients. It has been shown that autophagy, an evolutionarily conserved catabolic process that involves degradation of unnecessary or harmful cellular components via lysosomes, is induced following TKI treatment in CML cells. Of clinical importance, autophagy inhibition, using the anti-malarial drug hydroxychloroquine (HCQ), sensitised CML cells, including primitive CML stem cells, to TKI treatment. In this review we discuss the role of autophagy in the maintenance and survival of stem cells in more detail, with a focus on its role in survival of CML stem cells and the possibility to inhibit this pathway as a way to eliminate persistent CML stem cells in vitro and in patients.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / therapeutic use*
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Autophagy / drug effects*
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Cell Survival / drug effects
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Drug Design
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / enzymology
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
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Molecular Targeted Therapy
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Neoplastic Stem Cells / drug effects*
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Neoplastic Stem Cells / enzymology
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Neoplastic Stem Cells / pathology
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / therapeutic use*
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Protein-Tyrosine Kinases / metabolism
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Signal Transduction / drug effects
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Protein-Tyrosine Kinases