Masoome Bakhshayesh - Genetic department, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Ladan Hosseini Gohari - Cellular & Molecular Research Center, Medical Laboratory Science Department, School ofAllied Medicine, Iran University of Medical Sciences, Tehran, Iran
Mahmood Barati - Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences,Tehran, Iran
Majid Safa - Cellular & Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

The BCR-ABL oncogene is a tyrosine kinase gene that is over-expressed in CML. It prevents the TGF-β۱signaling pathway. Due to the resistance of cells to the tyrosine kinase inhibitor, STI-۵۷۱, the combinedeffect of STI-۵۷۱ and TGF-β۱ on K۵۶۲ cells was studied in the present research. Results revealed that thecaptured TGF-β۱ cell signaling pathway, which is activated in treated K۵۶۲ cells with TGF-β۱ activatesthe collective cell signaling pathways involved in survival and apoptosis.It is noteworthy that in K۵۶۲ cells treated with STI-۵۷۱, apoptotic pathways were triggered, accompaniedby the reduction of proteins such as Bcl-xL, Bcl-۲, p-AKT, p-Stat۵, p-FOXO۳, and Mcl-۱, and theenhancement of the pro-apoptotic proteins, PARP cleavage, and p۲۷, which led to the increase of sub-G۱phase arrested- and Annexin-positive cells.Interestingly, TGF-β۱ induced cells proliferation behavior was changed with the combination therapy, andalso STI-۵۷۱-induce apoptosis was prompted by this combination. Thus, it appears to cause theadvancement of the sub-G۱ cell cycle arrest, compared to treated cells individually. Furthermore, itstrongly triggered apoptosis signaling. In conclusion, TGF-β۱ did not negatively affect the STI-۵۷۱ effect,according to the results of positive annexin cells, and AKT protein phosphorylation has been effective inapoptosis.

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; transforming growth factor beta۱;Drug resistance; Apoptosis