A recent study confirmed that KCL22R cells also have an elevated growth rate and resistance to apoptosis. it has been shown that 1 uM imatinib induces a marked loss of Bcr Abl phosphorylation and of the overall expression of phosphotyrosine proteins in LAMA84 cells compared with K562 and KCL22S cells. This observation shows that KCL22 and K562 cells have an intrinsic resistance to imatinib, probably probably linked to the expression of several proteins implicated in drug resistance and anti apoptotic activity. angiogenesis inhibitors More over, KCL22S cells have characteristics typical of the quiescent hematopoietic Ph stem cells. In line with this statement, it’s been proven that imatinib, in combination with a farnesyltransferase inhibitor, induced KCL22S progress arrest but apoptosis was less apparent in KCL22 cells than in other CML cells. In still another study, autophosphorylation of Bcr Abl in KCL22R cells was suppressed by imatinib, as occurs in KCL22S cells, which suggests that KCL22R cells have developed an alternative solution opportinity for success that could bypass reliance on the primary oncoprotein action. Finally, imatinib did not produce Bcr Abl up regulation or an increased tolerance for tyrosine kinase inhibition in cells. KCL22 cells are thus a great product with which to get insights into the Bcr Abl independent systems of imatinib resistance. It’s significant that a drug may exert pleiotropic effects on the variety of different proteins thus leading Inguinal canal to alterations in protein expression, post translational modifications, and protein?protein interactions. Recent studies have examined the effects of imatinib on global protein expression and on global protein phosphorylation in Bcr Abl positive cell lines. It has been proven that the appearance of several proteins involved in energy transduction, protein activity, sign transduction, legislation, differentiation and apoptosis is differentially modulated by imatinib in CML sensitive cells and CML resistant. These findings c-Met inhibitor coincide with the statement that, after imatinib therapy, sensitive and painful cells undergo apoptosis while resistant cells survive. Many proteins that could be linked to signal transduction pathways have been shown to be downregulated in K562 delicate cells after treatment, which implies that the constitutively expressed Bcr Abl and its downstream signal transduction pathway are suppressed by imatinib. In comparison, the same research demonstrated that in resistant cells, proteins associated to signal transduction, such as for example serine/threonine protein kinase 13, which will be associated with protein phosphorylation, were up regulated after treatment. This observation suggests that if the Bcr Abl tyrosine kinase is inhibited, alternative pathways can preserve K562R cell survival.