Use and limitations of imatinib mesylate (Glivec), a selective inhibitor of the tyrosine kinaseAbl transcript in the treatment of chronic myeloid leukaemia.

Use and limitations of imatinib mesylate (Glivec), a selective inhibitor of the tyrosine kinaseAbl transcript in the treatment of chronic myeloid leukaemia. Br J Biomed Sci. 2004 Jan;61(2):103-111 Authors: Knight GWA, Mclellan D Abstract Chronic myeloid leukaemia is associated with a specific translocation between chromosomes 9 and 22 that results in the formation of a chimaeric gene. This gene, when transcribed, produces the BCR-Abl oncoprotein which has tyrosine kinase activity and the ability to prevent apoptosis, but has no effect on cellular proliferation. Imatinib mesylate, an inhibitor of the BCR-Abl transcript modelled on the ATP binding pocket of the Abl oncoprotein, prevents phosphorylation of effector molecules and induces apoptosis. Imatinib has limited effectiveness when BCR-Abl cells are in the quiescent cell-cycle state of G0. A life-long regimen of imatinib should reduce the risk of relapse from cells leaving G0. Up-regulation of BCR-Abl expression, ATP binding pocket mutations, up-regulation of MDR1 and over-expression of Pgp are all thought to limit the effectiveness of imatinib. Advanced BCR-Abl positivity is associated with complex mutations, which are thought to have a cumulative effect on the BCR-Abl oncoprotein in disrupting normal signal transduction, making these cells refractory to monotherapy alone. Combination therapy is thought to overcome this. Research studies have identified imatinib as a potential tre...
Source: British Journal of Biomedical Science - Category: Laboratory Medicine Tags: Br J Biomed Sci Source Type: research