1. ¹Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA
2. ²Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Mayer 557, Boston, MA, USA
3. ³Department of Cancer Discovery, ChemGenex Pharmaceuticals, Inc., Menlo Park, CA, USA

Correspondence: Dr S Li, Department of Medicine, University of Massachusetts Medical School, Lazare Research Building no. 315, 364 Plantation Street, Worcester, MA 01605, USA. E-mail: Shaoguang.Li@umassmed.edu

Received 10 October 2008; Revised 12 February 2009; Accepted 13 February 2009; Published online 26 March 2009.

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.