慢性粒细胞白血病（CML）在我国慢性白血病中发病率最高，目前临床应用酪氨酸激酶抑制剂治疗易耐药，复发风险高，而分化诱导疗法毒副作用低，已经在治疗急性早幼粒细胞白血病上取得瞩目成果。然而分化诱导疗法在治疗CML中的作用及机制研究未见报道。课题组前期研究发现，汉黄芩素能够通过上调GATA-1表达诱导CML细胞系发生红系分化并抑制细胞生长；近期文献报道汉黄芩素具有CDK9抑制活性，而CDK9参与构成的P-TEFb复合物在红系/巨核系定向分化调控中发挥关键作用。本项目旨在结合CML临床样本分析，探索CDK9活性与细胞红系分化潜能的关联性，阐明P-TEFb复合物和GATA-1的信号交联调控机制和汉黄芩素的诱导红系分化作用机理。同时本项目还根据CML原代细胞来源的CD34+CML干/定向祖细胞对汉黄芩素的应答来评价红系分化诱导策略在抗CML药物研发中的应用前景，为天然产物抗白血病研究提供新思路。

The incidence of CML is highest in chronic leukemia. Tyrosine kinase inhibitors are applied clinically with high risk of resistant and relapse. Differentiation induction therapy has low toxic and side effect and has made remarkable achievements in the treatment of acute promyelocytic leukemia. However, differentiation strategy hasn’t been successfully applied in the treatment of CML with rarely investigation on it. The previous research by our research group found that wogonin could induce erythroid differentiation of CML cells and inhibit cell growth, which is related to the up-regulation of GATA-1 expression. It has been reported that wogonin shows CDK9 inhibitor activity. CDK9 constitutes the P-TEFb complex which plays key role in erythroid / megakaryocytic differentiation conversion point. This project aims to clarify regulation mechanism of cross-talk of P-TEFb complex and GATA-1 contributing to wogonin-induced erythroid differentiation. Also the project study the correlation between CDK9 activity of CML cells and erythroid differentiation, and response of CML stem/progenitor cells to wogonin, to evaluate the application prospect of erythroid differentiation strategy in the research and development of anti-CML drugs discovery, to provide a new idea of anti-leukemia research of natural products.