伊马替尼是治疗慢性粒细胞白血病（CML）的一线药物，其耐药的产生是CML进展及治疗失败的重要原因，但耐药机制尚未完全阐明。我们前期实验发现耐伊马替尼细胞K562G外泌体可促进K562对伊马替尼产生耐药,该外泌体携带高浓度miR-365，生物信息学分析显示其靶基因包含BAX等促凋亡基因。据此，我们提出“耐伊马替尼CML细胞通过外泌体递送转运miR-365促进耐药的发生”的假说。我们拟通过激光共聚焦显微镜检查、流式细胞术、非接触共培养等实验证实K562G通过释放外泌体促进耐药发生；通过荧光素酶实验、过表达及抑制实验、RT-PCR及蛋白印迹等分子生物学实验证实外泌体的促进耐药作用是通过其携带的miR-365下调K562相关促凋亡分子表达而实现的。最终证实耐伊马替尼CML可以通过释放外泌体对肿瘤微环境进行改造，为进一步阐述CML耐药机制及提高CML疗效提供理论基础。

Imatinib is the first-line drug of treating chronic myeloid leukemia(CML),and the emergence of drug resistance is an important reason for the CML progression and treatment failure, but the mechanism has not been fully elucidated. Our previous experiments found that the Imatinib resistant K562G –derived exosomes can promote K562 of imatinib resistance, the exosomes carried high concentrations of mir-365, biological information science analysis showed that the target gene contains Bax and other pro apoptotic gene. Accordingly, we propose the hypothesis that the imatinib resistant CML cells derived-exosomes can delivery and transport miR-365 to promote drug resistance. We try to confirm that K562G cells can release exosomes to promote drug resistance by laser confocal microscopy, flow cytometry, non-contact co culture experiments; and confirm that the resistance effect is induced by miR-365 delivered by exosomes from K562G cells by luciferase assays, overexpression and inhibition assay, RT-PCR, Western blot and other molecular biology experiments. Finally, we confirm the imatinib-resistant CML cells can release exosomes and reform tumor microenvironment to transform the resistance properties, and further explain the mechanism of drug resistance of CML and provide a theoretical basis to improve the CML therapy.