Differential tyrosine phosphorylation of leukemic cells during apoptosis as a result of treatment with imatinib mesylate.

Posted by rob on September 26, 2005 under Uncategorized | Be the First to Comment

Park J, Kim S, Oh C, Yoon SS, Lee D, Kim Y

Biochem Biophys Res Commun. 2005 Oct 28; 336(3): 942-51

Bcr-Abl fusion tyrosine kinase contributes to leukemic transformation. Imatinib mesylate inhibits Bcr-Abl tyrosine kinase, resulting in a blockage of tyrosine phosphorylation in its downstream pathways. We analyzed the alteration of tyrosine phosphorylation, on BCR/ABL(+) chronic myelogenous leukemia cells, after treatment with imatinib mesylate. Data were collected using a two-dimensional gel electrophoresis followed by Western blot and mass spectrometry. The inhibition of Bcr-Abl tyrosine kinase by 2.5muM imatinib mesylate caused both cell cycle arrest in the G(0)/G(1) phase and increased the portion of apoptotic cells. As a result, the population of leukemic cells decreased by 30% and 70% compared to controls at 24 and 72h, respectively. Furthermore, treatment with imatinib mesylate altered tyrosine phosphorylation of 24 protein spots as the incubation time proceeded from 0 to 24 and 72h. Ten of the 24 protein spots are visible at all three times. Four are detectable at both the 0 and 24h points in time. Eight were detectable only at time 0.Differential tyrosine phosphorylation of leukemic cells during apoptosis as a result of treatment with imatinib mesylate.