Hekmatshoar, YaldaÖzkan, TülinKarabay, Arzu ZeynepBozkurt, SüreyyaKaradağ Gürel, AynurKurnaz Gömleksiz, ÖzlemFışgın, TunçSunguroğlu, Asuman2025-10-162025-10-162025Hekmatshoar, Y., Ozkan, T., Karabay, A. Z., Bozkurt, S., Gurel, A. K., Gomleksiz, O. K., ... & Sunguroglu, A. (2025). Targeting Integrin α2 to Overcome Imatinib Resistance in Chronic Myeloid Leukemia Cells. Biomolecules, 15(9), 1245. 10.3390/biom150912452218-273Xhttps://hdl.handle.net/20.500.12939/5962Chronic myeloid leukemia (CML) is a blood disorder caused by a genetic alteration that creates the BCR-ABL fusion gene, leading to continuous activation of cell growth signals and uncontrolled proliferation of the blood cells. Imatinib (IMA) resistance remains a major obstacle in CML treatment. Integrins, particularly integrin α2 (ITGA2), have been associated with cancer progression and drug resistance. In the current study, we investigated the role of ITGA2 in IMA resistance using IMA-sensitive K562 (K562S) and IMA-resistant K562 (K562R) cells. Our findings showed that ITGA2 is overexpressed in K562R cells and ITGA2 inhibitor E7820 (2.5 µM) treatment significantly decreased cell viability and induced apoptosis in both sensitive and resistant cells. Combination treatment with E7820 and imatinib enhanced pro-apoptotic gene expression (BAX, BIM) and decreased anti-apoptotic BCL2 levels in imatinib-resistant K562R cells. Flow cytometry confirmed ITGA2 inhibition at the protein level, and rhodamine assays revealed reduced MDR1 activity in treated cells. These results demonstrate that targeting ITGA2 may overcome imatinib resistance and offer a novel therapeutic strategy for CML.eninfo:eu-repo/semantics/openAccessE7820apoptosischronic myeloid leukemiaimatinib resistanceintegrin α2Article10.3390/biom15091245159410085522-s2.0-105017408431Q1WOS:001580368900001Q1