Inhibitory effects of omacetaxine on leukemic stem cells and BCR-ABL-induced chronic myeloid leukemia and acute lymphoblastic leukemia in mice
UMass Chan Affiliations
Department of Medicine, Division of Hematology/OncologyDocument Type
Journal ArticlePublication Date
2009-03-27Keywords
AnimalsAntineoplastic Agents, Phytogenic
Cell Line, Tumor
Fusion Proteins, bcr-abl
Gene Expression Regulation, Leukemic
HSP90 Heat-Shock Proteins
Harringtonines
Humans
K562 Cells
Leukemia, B-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Neoplastic Stem Cells
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Radiation Chimera
Recombinant Fusion Proteins
Transduction, Genetic
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
Leukemia. 2009 Aug;23(8):1446-54. Epub 2009 Mar 26. Link to article on publisher's site
DOI
10.1038/leu.2009.52Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39376PubMed ID
19322212Related Resources
ae974a485f413a2113503eed53cd6c53
10.1038/leu.2009.52
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