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 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 demonstrated 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% B220+leukemia cells were found in peripheral blood, compared with 34% B220+leukemia cells in the placebo group. Treatment with omacetaxine decreased the number of leukemia stem cells and prolonged survival of mice with BCR-ABL induced CML or B-ALL.
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