Src kinase signaling in leukaemia.


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Antineoplastic-Agents, Cell-Survival, Enzyme-Activation, Gene-Expression-Regulation-Leukemic, Genes-abl, Humans, Mice, Neoplastic-Stem-Cells, Piperazines, Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma, Pyrimidines, Signal-Transduction, src-Family-Kinases

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Int J Biochem Cell Biol 2007; 39(7-8):1483-8.


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.