Autophagy in Chronic Myeloid Leukaemia: Stem Cell Survival and Implication in Therapy
Gudmundur V. Helgason,
Tessa L. Holyoake.
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.
Keywords: Autophagy, Bcr-Abl, CML, clinical trials, glioblastoma, haemopoietic stem cells, HCQ, ROS.
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