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Targeting Chronic Myeloid Leukemia Stem Cells

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Abstract

Chronic myeloid leukemia (CML) arises as a consequence of a chromosomal translocation giving rise to the Philadelphia chromosome and Bcr-Abl oncogene. CML is a clonal disease of stem cell origin and an excellent example of a malignancy in which tumor-initiating cells may hold the key to disease eradication. The known molecular basis of CML has enabled the development of Abl-specific tyrosine kinase inhibitors, such as imatinib mesylate. However, the success of tyrosine kinase inhibitors, as rationally designed first-line therapies, has been tempered by problems of disease persistence and resistance. Residual disease has been shown to be enriched within the stem cell compartment and to persist at stable levels for up to 5 years of complete cytogenetic response. This finding has led to further searches for novel strategies aimed at eliminating these cells; such strategies may be essential in achieving cure. The most significant recent findings are discussed in this review.

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Acknowledgments

We would like to thank Dr. Mhairi Copland for providing FACS plots for Fig. 1.

Disclosure

Dr. Holyoake has received research funding and honoraria for consultancy from Novartis and Bristol-Myers Squibb. No other potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. Paul O’Gorman Leukaemia Research Centre, Faculty of Medicine, Gartnavel General Hospital, University of Glasgow, 21 Shelley Road, G12 0XB, Glasgow, UK

    G. Vignir Helgason, Graham A. R. Young & Tessa L. Holyoake

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  1. G. Vignir Helgason
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  2. Graham A. R. Young
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  3. Tessa L. Holyoake
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Correspondence to Tessa L. Holyoake.

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Helgason, G.V., Young, G.A.R. & Holyoake, T.L. Targeting Chronic Myeloid Leukemia Stem Cells. Curr Hematol Malig Rep 5, 81–87 (2010). https://doi.org/10.1007/s11899-010-0043-0

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