Glivec Research Today is a free monthly online journal that collates and summarizes the latest research about Glivec, including details on gleevec, imatinib, cancer, treatment, side-effects.

Adaphostin and bortezomib induce oxidative injury and apoptosis in imatinib mesylate-resistant hematopoietic cells expressing mutant forms of Bcr/Abl.

Dasmahapatra G, Nguyen TK, Dent P, Grant S

Department of Medicine, Virginia Commonwealth University/Massey Cancer Center, Richmond, VA 23298, USA.

Effects of the tyrphostin adaphostin and bortezomib were examined in Bcr/Abl+ leukemia cell resistant to imatinib mesylate secondary to Bcr/Abl point mutations. Adaphostin was equally effective in inducing mitochondrial damage, caspase activation, JNK activation, and Raf-1, phospho-Stat3 and -Stat5 inactivation in mutant and wild-type cells, but differentially down-regulated phospho-Bcr/Abl. Adaphostin and bortezomib synergistically induced apoptosis in wild-type and mutant cells, including T315I mutants. Notably, adaphostin+/-bortezomib potently induced ROS and lethality in mutant cells, effects attenuated by the antioxidant NAC. These findings indicate that adaphostin+/-bortezomib circumvent imatinib resistance due to Bcr/Abl point mutations most likely through ROS generation.

Published 21 August 2006 in Leuk Res, 30(10): 1263-72.
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