Hekmatshoar Yalda, Ozkan Tulin, Karabay Arzu Zeynep, Bozkurt Sureyya, Gurel Aynur Karadag, Gomleksiz Ozlem Kurnaz, Fisgin Tunc, Sunguroglu Asuman
Department of Medical Biology, School of Medicine, Altinbas University, 34147 Istanbul, Turkey.
Department of Medical Biology, School of Medicine, Ankara University, 06230 Ankara, Turkey.
Biomolecules. 2025 Aug 28;15(9):1245. doi: 10.3390/biom15091245.
Chronic myeloid leukemia (CML) is a blood disorder caused by a genetic alteration that creates the 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 (), have been associated with cancer progression and drug resistance. In the current study, we investigated the role of in IMA resistance using IMA-sensitive K562 (K562S) and IMA-resistant K562 (K562R) cells. Our findings showed that 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 (, ) and decreased anti-apoptotic 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 may overcome imatinib resistance and offer a novel therapeutic strategy for CML.
慢性粒细胞白血病（CML）是一种由基因改变引起的血液疾病，该基因改变产生融合基因，导致细胞生长信号持续激活和血细胞不受控制的增殖。伊马替尼（IMA）耐药性仍然是CML治疗中的主要障碍。整合素，特别是整合素α2（），与癌症进展和耐药性有关。在本研究中，我们使用对IMA敏感的K562（K562S）和对IMA耐药的K562（K562R）细胞研究了在IMA耐药中的作用。我们的研究结果表明，在K562R细胞中过表达，ITGA2抑制剂E7820（2.5 μM）处理显著降低了敏感和耐药细胞的细胞活力并诱导了细胞凋亡。E7820和伊马替尼联合治疗增强了对伊马替尼耐药的K562R细胞中促凋亡基因的表达（，）并降低了抗凋亡水平。流式细胞术在蛋白质水平证实了ITGA2的抑制作用，罗丹明测定显示处理细胞中MDR1活性降低。这些结果表明，靶向可能克服伊马替尼耐药性，并为CML提供一种新的治疗策略。
