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

被引：33
|
作者：
Helgason, Gudmundur V. [1 ]
Mukhopadhyay, Arunima [1 ]
Karvela, Maria [1 ]
Salomoni, Paolo [2 ]
Calabretta, Bruno [3 ]
Holyoake, Tessa L. [1 ]
机构：
[1] Univ Glasgow, Inst Canc Sci, Coll Med Vet & Life Sci, Paul OGorman Leukaemia Res Ctr, Glasgow G12 0ZD, Lanark, Scotland
[2] UCL, Inst Canc, Samantha Dickson Brain Canc Unit, London WC1E 6BT, England
[3] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA
来源：
CURRENT CANCER DRUG TARGETS | 2013年 / 13卷 / 07期
基金：
英国医学研究理事会;
关键词：
Autophagy; Bcr-Abl; CML; clinical trials; glioblastoma; haemopoietic stem cells; HCQ; ROS; CHRONIC MYELOGENOUS LEUKEMIA; BCR-ABL; KINASE-ACTIVITY; TARGETING AUTOPHAGY; HEMATOPOIETIC PROGENITORS; PRIMARY CML; INHIBITION; IMATINIB; QUIESCENT; MITOCHONDRIA;
D O I：
10.2174/15680096113139990088
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：724 / 734
页数：11
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