c-ABL是一个重要的酪氨酸蛋白激酶，与慢性髓细胞性白血病的发生密切相关。c-ABL特异性酪氨酸激酶抑制剂imatinib已成为临床广泛使用的CML一线治疗药物。然而，imatinib的耐药性成为CML治疗面临的新问题。本项目前期研究发现PLK1是c-ABL的一个重要的激酶底物。c-ABL可以与PLK1相互作用并磷酸化PLK1，促进细胞G2/M转换及增殖。更为重要的是，我们发现c-ABL介导的PLK1过表达与白血病患者的imatinib耐药性正相关。本项目将采用分子生物学及细胞生物学等方法，主要进行以下内容的研究：1）研究c-ABL调控PLK1蛋白水平及激酶活性的分子机制；2）研究c-ABL介导的PLK1磷酸化的细胞生物学功能；3）探究c-ABL-PLK1调控在CML化疗应答中的作用。本研究不但可以进一步拓展人们对细胞周期调控机制的认识，而且可能为CML的治疗提供新的组合用药策略。

BCR-ABL tyrosine-kinase inhibitors (TKI) are the first-line therapy for most patients with chronic myelogenous leukemia (CML). Nevertheless, resistance or tolerance to imatinib and other BCR/ABL inhibitors may occur during therapy, and the underlying mechanisms remain largely elusive. In our previous study, we found that Polo-like kinase-1 (PLK1) is an important downstream target of c-ABL/ BCR-ABL. Moreover, PLK1 overexpression is correlated with imatinib resistance in CML patients.In this project, we plan to study: 1) The functions of c-ABL-PLK1 axis in cancer cell growth, 2） How does c-ABL regulate PLK1 function? 3) Does PLK1 represent a novel target in imatinib-resistance CML? We truly believe our project represents a major issue in the field and will provide an effective approach for CML therapy.