微小残留白血病(MRD)是引起慢性粒细胞白血病（CML）耐药和复发的主要原因，也是攻克血液肿瘤的难点和重点。大量研究表明过度激活STAT5参与CML耐药，但其介导耐药的分子机制尚未系统性阐明。前期结果表明骨髓微环境中伊马替尼（IM）并不能完全抑制CML细胞p-STAT5Tyr694表达，同时明显升高CML CD34+亚群比例。因此设想IM作用下STAT5激活是否与CML CD34+亚群存活有关？本项目拟建立SM-DR耐药模型和NSG小鼠血液瘤模型，以STAT5为切入点，体内外探讨IM作用下STAT5激活与骨髓微环境诱导CML CD34+细胞耐药关系，并从JAK2/STAT5信号通路系统性阐述STAT5如何参与CMLCD34+细胞耐药过程。同时，本研究还通过考察黄芩素在这一机制中逆转耐药作用，从反向角度进一步综合评价其分子机制，为阐明MRD耐药机制及靶向治疗药物的开发提供新方向。

Minimal residual disease (MRD) is the main source of resistance and relapse in chronic myeloid leukemia (CML), is also difficulties and emphases to overcome blood cancer. A large number of researches have shown that constitutive Stat5 activation enhanced chemotherapeutic resistance in CML, but its molecular mechanism of drug resistance has not been systematically elucidated. Previous research results suggested that imatinib (IM) did not completely inhibit the expression of p-STAT5Tyr694 in bone marrow microenvironment, and upregulated the proportion of CD34+subpopulation in CML cells. Therefore, it is assumed that STAT5 activation is associated with survival of CML CD34+ subpopulation within IM? To investigate the relationship between STAT5 activation and bone marrow microenvironment-induced resistance in CML CD34+cells in vivo and in vitro, we established SM-DR resistance model and NSG mouse hematoma model respectively. Meanwhile, we aimed to clarify how STAT5 contributed to resistance in CMLCD34+ cell from JAK2 / STAT5 signaling pathway systematically. At the same time, Baicalein was used to examine the reversal effect based on the resistant mechanism to further evaluate its molecular mechanism on the contrary sides. This study provided a new direction for elucidating the mechanism of MRD resistance and new target-drug development for MRD resistance.