尿激酶型纤溶酶原激活物系统与急性髓细胞白血病关系的研究进展

Research Progress of Relationship Between Urokinase Plasminogen Activator System and Acute Myelocytic Leukemia

尿激酶型纤溶酶原激活物系统(urokinase plasminogen activator system,u PAs)在急性髓细胞白血病(acute myelocytic leukemia,AML)发生、发展过程中的作用已成为当前临床研究关注的热点。尿激酶型纤溶酶原激活物(u PA)与其受体(u PAR,又称CD87)结合促使纤溶酶原激活为纤溶酶,这一过程受到u PAs的两种主要抑制剂纤维蛋白溶酶原激活物抑制物(plasminogen activator inhibitor,PAI)PAI-1和PAI-2的调控。激活的纤溶酶一方面导致细胞外基质及基底膜的降解,另一方面增加基质金属蛋白酶原(Pro-matrix metalloproteinases,Pro-MMP)及生长因子(growth factor,GF)的激活,促进AML细胞髓外浸润、转移及增殖。并且u PAs作为纤溶系统的重要成分之一,其表达的上调导致纤溶亢进,增加AML患者发生出血的风险。本文对u PAs的结构及其在AML发生发展和治疗中的作用进行综述。

Currently, the role of urokinase plasminogen activator system（u PAs） in the occurrence and development of acute myelocytic leukemia（AML） has become a hot topic in clinical researches. The association of u PA to its receptor triggers the conversion of plasminogen into plasmin. This process is regulated by the u PA inhibitors（PAI-1 and PAI-2）. On one hand, the activated plasmin promotes the degradation of basement membrane and extracellular matrix（ECM） components; on the other hand, it could activate ECM pro-matrix metalloproteinases（Pro-MMP） and growth factor（GF）, thus contributing to the leukaemic cells extramedullary disseminations, metastasizing and proliferation. What’s more, as one of the main components of fibrinolytic system, u PAs over-expression is associated with hyperfibrinolysis, leading to increased bleeding complications. This paper mainly summarizes the structure of u PAs and its contribution to the occurrence, development as well as treatment of AML.