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Chronic Myeloproliferative Neoplasias

Inhibitory effects of omacetaxine on leukemic stem cells and BCR-ABL-induced chronic myeloid leukemia and acute lymphoblastic leukemia in mice

Leukemia volume 23, pages 1446–1454 (2009)Cite this article

Abstract

Omacetaxine mepesuccinate (formerly homoharringtonine) is a molecule with a mechanism of action that is different from tyrosine kinase inhibitors, and its activity in chronic myeloid leukemia (CML) seems to be independent of the BCR-ABL mutation status. Using BCR-ABL-expressing myelogenous and lymphoid cell lines and mouse models of CML and B-cell acute lymphoblastic leukemia (B-ALL) induced by wild-type BCR-ABL or T315I mutant-BCR-ABL, we evaluated the inhibitory effects of omacetaxine on CML and B-ALL. We showed that more than 90% of the leukemic stem cells were killed after treatment with omacetaxine in vitro. In contrast, less than 9 or 25% of the leukemic stem cells were killed after treating with imatinib or dasatinib, respectively. After 4 days of treatment of CML mice with omacetaxine, Gr-1+myeloid leukemia cells decreased in the peripheral blood of the treated CML mice. In the omacetaxine-treated B-ALL mice, only 0.8% of the B220+leukemia cells were found in peripheral blood, compared with 34% of the B220+leukemia cells in the placebo group. Treatment with omacetaxine decreased the number of leukemia stem cells and prolonged the survival of mice with BCR-ABL-induced CML or B-ALL.

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Acknowledgements

This work is supported by grants from the Leukemia & Lymphoma Society and the National Institutes of Health (R01-CA114199, R01-CA122142) to SL. SL is a Scholar of the Leukemia and Lymphoma Society.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

    Y Chen & S Li

  2. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Mayer 557, Boston, MA, USA

    Y Hu

  3. Department of Cancer Discovery, ChemGenex Pharmaceuticals, Inc., Menlo Park, CA, USA

    S Michaels, D Segal & D Brown

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  1. Y Chen
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Correspondence to S Li.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Chen, Y., Hu, Y., Michaels, S. et al. Inhibitory effects of omacetaxine on leukemic stem cells and BCR-ABL-induced chronic myeloid leukemia and acute lymphoblastic leukemia in mice. Leukemia 23, 1446–1454 (2009). https://doi.org/10.1038/leu.2009.52

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