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Chronic Myeloid Leukemia Stem Cells

Edward Kavalerchik, Daniel Goff, Catriona H.M. Jamieson

From the University of California San Diego (UCSD) School of Medicine, Department of Medicine, Division of Hematology-Oncology, Rebecca and John Moores UCSD Cancer Center, San Diego, CA

Corresponding author: Edward Kavalerchik, MD, Division of Hematology-Oncology, Department of Internal Medicine, Moores Cancer Center, 3855 Health Science Rd, University of California –San Diego, San Diego, CA 92093-0820; e-mail: ekavalerchik{at}ucsd.edu

Although rare, chronic myeloid leukemia (CML) represents an important paradigm for understanding the molecular events leading to malignant transformation of primitive hematopoietic progenitors. CML was the first cancer to be associated with a defined genetic abnormality, BCR-ABL, that is necessary and sufficient for initiating chronic phase disease as well as the first cancer to be treated with molecular targeted therapy. Malignant progenitors or leukemia stem cells (LSCs) evolve as a result of both epigenetic and genetic events that alter hematopoietic progenitor differentiation, proliferation, survival, and self-renewal. LSCs are rare and divide less frequently, and thus, represent a reservoir for relapse and resistance to a molecularly targeted single agent. On subverting developmental processes normally responsible for maintaining robust life-long hematopoiesis, the LSCs are able to evade the majority of current cancer treatments that target rapidly dividing cells. Enthusiasm for the enormous success of tyrosine kinase inhibitors at controlling the chronic phase disease is tempered somewhat by the persistence of the LSC pool in the majority of the patients. Combined therapies targeting aberrant properties of LSC may obviate therapeutic resistance and relapse in advanced phase and therapeutically recalcitrant CML.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.