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CANCER STEM CELLS

Chronic Myeloid Leukemia Blast Crisis Arises from Progenitors

Society of Fellows, Harvard University, Cambridge, Massachusetts, USA, and Dana Farber Cancer Institute, Boston, Massachusetts, USA

Key Words. Chronic myeloid leukemia • Hematopoietic stem cells • Hematopoietic progenitor cells • Differentiation

Correspondence: Franziska Michor, Ph.D., Harvard University, Society of Fellows, 78 Mt Auburn Street, Cambridge, Massachusetts 02138, USA. Telephone: 617-495-2485; Fax: 617-495-2645; e-mail: michor{at}fas.harvard.edu

Received October 9, 2006; accepted for publication January 2, 2007.
First published online in STEM CELLS EXPRESS   January 11, 2007.



Chronic myeloid leukemia (CML) progresses through three distinct clinical stages: chronic phase, accelerated phase, and blast crisis. The progression to accelerated phase and blast crisis is driven by activation of oncogenes, inactivation of tumor suppressor genes, and/or amplification of the BCR-ABL fusion gene, which causes the chronic phase of the disease. The cell of origin of blast crisis is a subject of speculation. Here, I develop a simple mathematical model of CML blast crisis to investigate whether blasts arise from leukemic stem cells or more differentiated leukemic cells. I use data of patients treated with imatinib and previous agents to estimate the effects of therapy on the rate of progression. Imatinib reduces the progression rate 10-fold as compared with previous (ineffective) therapies. If blasts were produced by leukemic stem cells, there would be no difference in the rate of progression between patients treated with imatinib and previous therapies, because imatinib seems to be incapable of depleting leukemic stem cells. Imatinib does, however, deplete leukemic progenitors. Therefore, CML blasts are likely to arise from leukemic progenitors.

Disclosure of potential conflicts of interest is found at the end of this article.

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