The affect of the tirosine kinase inhibitors on the autophagic cell death in the BCR-ABL positive cells

Better understanding of programmed cell death mechanisms is important for determining treatment strategies and designing drugs in which there is a disorder in the cell death mechanisms. Today different types of programmed cell death are identified. In chronic myelogenous leukemia (CML), the resistance toward programmed cell death caused by the BCR-ABL chimeric gene product which is a tyrosine kinase was revealed in the late 1990s and was confirmed in the following studies. Studies are done on the efficacy of drugs inducing apoptosis. Molecular mechanisms of many anticancer drugs are focused on apoptosis including İmatinib which is used in CML. Their efficacy on other types of programmed cell death are not yet determined. Our primary research goal is to ivestigate the role of other forms of cell death in CML biology and in resistance to therapy. This present study is the part of our prelimenary work focusing on the development of a imatinib resistant K562 clon. We applied increasing doses of imatinib to the K-562 chronic myeloid leukemia cell line and we obtained imatinib-resistant subclons. İmatinib resistance was confirmed by annexin-V staining and caspase-3 activation analyses.