Abstract
Role of Src kinases in acute lymphoblastic leukaemia has been recently demonstrated in leukaemia mouse model. Retained activation of Src kinases by the BCR-ABL oncoprotein in leukaemic cells following inhibition of BCR-ABL kinase activity by imatinib indicates that Src activation by BCR-ABL is independent of BCR-ABL kinase activity and provides an explanation for reduced effectiveness of the BCR-ABL kinase activity inhibitors in Philadelphia chromosome-positive acute lymphoblastic leukaemia. Simultaneous inhibition of kinase activity of both BCR-ABL and Src kinases results in long-term survival of mice with acute lymphoblastic leukaemia. Leukaemic stem cells exist in acute lymphoblastic leukaemia, and complete eradication of this group of cells would provide a curative therapy for this disease.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Review
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Benzamides
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Cell Survival / drug effects
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Enzyme Activation
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Gene Expression Regulation, Leukemic
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Genes, abl / physiology*
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Humans
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Imatinib Mesylate
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Mice
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Neoplastic Stem Cells / cytology*
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Piperazines / pharmacology
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Piperazines / therapeutic use*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / enzymology*
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Pyrimidines / pharmacology
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Pyrimidines / therapeutic use*
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Signal Transduction*
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src-Family Kinases / antagonists & inhibitors
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src-Family Kinases / physiology*
Substances
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Antineoplastic Agents
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Benzamides
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Piperazines
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Pyrimidines
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Imatinib Mesylate
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src-Family Kinases