An ongoing search for alternative or complementary approaches with the capacity of eliminating Bcr Abl leukemic cells resistant to available kinase inhibitors appears normal. The tyrphostin adaphostin, which is different from conventional tyrosine kinase inhibitors by virtue of its capability to inhibit peptide substrates as opposed to ATP, shows an attractive prospect such settings. For example, in Bcr/Abl leukemia cells, adaphostin was demonstrated to induce Bcr/Abl down dephosphorylation and regulation, in addition to apoptosis, price Dovitinib more quickly than imatinib mesylate, and to be considerably more active than the latter agent on a molar basis. Furthermore, adaphostin was effective against imatinib mesylate resistant K562 cells featuring about a 3 fold increase in Bcr/Abl protein levels. In a very recent survey, it was found that adaphostin causes cell death in cells expressing E255K and T315I point mutations by virtue of ROS generation. Our results are in line with these results, and moreover, extend them to add the M351T mutation; show Meristem that adaphostin efficiently induces mitochondrial damage in mutant cells; indicate that Bcr/Abl point mutations are unable to stop adaphostin from causing alterations in signaling pathways downstream of Bcr/Abl. It’s specially noteworthy that cells expressing the mutation, which confers resistance to the 2nd technology Bcr/Abl kinase inhibitors AMN107 and BMS 354825, remained fully sensitive and painful to adaphostin induced mitochondrial injury, perturbations in Stat3, Stat5, and JNK, together with lethality. While it is tempting to suppose that adaphostin acts by inhibiting mutant Bcr/Abl kinase, the available evidence argues from the possibility that this represents the sole process of activity in mutant cells. Specifically, while adaphostin exerted clearly divergent effects on Bcr/Abl phosphorylation position in wild type and mutant cells, ranging from pronounced down regulation in wild type cells angiogenesis inhibitors to minimal down regulation in T315I cells, it was equally effective in causing apoptosis in all the cell lines. Together, these findings suggest that the ability of adaphostin to destroy cells bearing Bcr/Abl mutations is unlikely to come exclusively or mainly from kinase dephosphorylation/ inhibition, but rather requires additional factors. Today’s results argue clearly that in these cells, adaphostin lethality stems mainly from induction of oxidative damage. Previous studies demonstrated that adaphostin eliminates equally Bcr/Abl and Bcr/Abl leukemia cells by enhancing ROS generation. There’s no a priori reason why mutant Bcr/Abl would be far better than wild type in this regard, while constitutive Bcr/Abl kinase initial up oversees anti apoptotic signaling proteins that may protect cells from oxidative damage.