findings suggest the clinical relevance of targeting Akt signaling in imatinib resistant individuals. Nonsteroidal anti inflammatory drugs and COX 2 inhibitors have now been investigated for cancer chemo-prevention and chemotherapy. There is also proof that COX 2 inhibitors might be successful in cells with minimal COX 2 expression and that several inhibitory responses on cell growth induced by these compounds are COX 2 independent. More over, COX 2 over expression induces the expression of MDR 1, which Afatinib clinical trial causes multi-drug resistance, suggesting that COX 2 inhibition may decrease the phenotype. Previous information showthat bone marrowCOX 2 levels are increased in chronic phaseCMLand are associated with paid off survival. The data presented here also reveal an expression of COX 2 and MDR 1 in immune cells, but not in-the sensitive and painful cells, and thus increasing the survival of those cells despite imatinib treatment at high levels. Celecoxib in the current study inhibited the expression of both COX Eumycetoma 2 and MDR 1, which can be responsible for the development of resistance, therefore sensitizing IR K562 cells to the cytotoxic effects of imatinib. The fact that NS 398, another COX 2 specific inhibitor, prevents the COX 2 mediated increase in MDR 1 expression and action supports such a possibility. In summary, our results give evidence that COX 2 and MDR 1 over expression have the effect of the develop-ment of resistance to imatinib in IR K562 cells and celecoxib, a selective COX 2 inhibitor, induces apoptosis of IR K562 cells by down regulating the expression ofCOX 2 and MDR1 by a system involving Akt pathway. This study suggests the use of celecoxib alongside imatinib in overcoming the drug resistance in imatinib resilient CML. As in many of the chromosomal translocations that bring about fusion protein, the BCR ABL fusion protein can be a constitutively active tyrosine kinase. Recently this BCR ABL fusion protein has been effectively targeted supplier Dabrafenib for therapy with a specific tyrosine kinase inhibitor, imatinib. Regardless of the success of the drug, an important portion of patients respond defectively or acquire resistance to imatinib therapy. Resistance to imatinib therapy has stimulated develop-ment of new, more specific kinase inhibitors such as BMS 354825 andAMN107that target resistant types of the BCR ABL protein. Monitoring recurring dis-ease inCMLpatients currently depends onRT PCR assay of BCR ABL mRNA, nevertheless the RT PCR assay gift suggestions inherent problems with standardizing and variability quantitation. Furthermore, it’s become increasingly important to have the ability to assay the experience of the BCR ABL protein in CML patients as a possible diagnostic tool to predict response or treatment, and as a means of monitoring efficacy and response to therapy.