细胞周期依赖性蛋白激酶及细胞周期蛋白D在血液系统恶性肿瘤中的作用

Role of cell cycle-dependent protein kinase and cyclin D in hematological malignancies

血液系统恶性肿瘤系突变的造血干细胞或前体祖细胞过度增殖，而正常造血系统被破坏的一组恶性肿瘤。正常细胞增殖受细胞周期依赖性蛋白激酶（CDK）严格调控，这些激酶不仅在细胞周期中发挥重要作用，还参与造血干细胞的自我更新与分化、表观遗传调节及DNA损伤修复等细胞活动。对于CDK基因敲除小鼠的研究发现，CDK表达缺失与肿瘤发生相关，而其染色体易位、基因突变引起的CDK表达改变均在肿瘤发生、发展中起作用，这也使更多的肿瘤研究聚焦在CDK及其靶向药物抑制剂的研究方面。细胞周期蛋白（cyclin）D可以与CDK形成CDK4／6-cyclinD复合体，参与造血干细胞细胞周期的调控。笔者拟就CDK、cyclinD及CDK4／6-cyclinD复合体在正常造血及血液系统恶性肿瘤的作用机制，以及CDK4／6靶向抑制剂在血液系统恶性肿瘤治疗中的应用的最新研究进展进行综述。

Hematologic malignancies are clonal hematologic disorders characterized by uncontrolled proliferation of mutational stem or progenitor cells, and the process of normal hematopoiesis is always disturbed. Normal cell cycle is tightly regulated by cyclin dependent kinases （CDK）. CDK not only plays an important role in cell cycle, but also in the self-renewal of stem ceils, epigenetic regulation and DNA repair. Studies of CDK gene knockout mouse models have demonstrated that CDK also is involved in the pathogenesis of cancers. Meanwhile the abnormal expression of CDK caused by chromosomal translocation or genetic mutations has been described in many tumors. That is why more and more attention is played on pharmacological inhibition targeted CDK. Cyclin D can form a CDK4/6-cyclin D complex with CDK, and participate in the regulation the cell cycle of hematopoietic stem cell. This article reviews roles of CDK, cyclin D and CDK4/6-cyclin D in hematopoiesis and hematologic malignancies, and the application of cell cycle inhibitors targeted CDK4/6-cyclin D in hematologic malignancies.