Autophagy in Chronic Myeloid Leukaemia:  Stem Cell Survival and Implication in Therapy

Gudmundur   V.   Helgason; Arunima      Mukhopadhyay; Maria      Karvela; Paolo      Salomoni; Bruno      Calabretta; Tessa   L.   Holyoake

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.

Keywords: Autophagy, Bcr-Abl, CML, clinical trials, glioblastoma, haemopoietic stem cells, HCQ, ROS.