急性白血病纤溶指标改变及其机制的研究

Study on the alterations of fibrinolysis and its mechanism in patients with acute leukemia

目的:研究不同类型急性白血病(AL)初诊时血浆组织型纤溶酶原激活剂(t-PA)、纤溶酶原激活剂抑制物-1(PAI-1)、纤维蛋白(原)降解产物(FDP)、纤溶酶原活性及AL细胞表面膜联蛋白Ⅱ(Ⅱ)和尿激酶型纤溶酶原激活剂受体(uPAR)的表达的变化,探讨AL纤溶指标改变及其机制。方法:选择初治AL患者63例,以MICM诊断分型分组,留取治疗前外周血浆标本和骨髓单个核细胞,分别以发色底物法和ELISA法检测患者血浆纤溶指标(纤溶酶原活性、t-PA:A、PAI-1:A、t-PA:Ag、PAI-1:Ag、FDP),流式细胞术检测AL细胞表面An-nexinⅡ和uPAR的表达,RT-PCR检测AL细胞AnnexinⅡ和uPAR的mRNA表达水平。结果:AL组PAI-1:A,PAI-1:Ag较正常对照组升高,纤溶酶原活性较正常对照组降低,M3组最低;t-PA:Ag、t-PA:A与正常对照无差异;急性髓系白血病(AML)组FDP含量较正常对照为高,M3组升高最为明显。AML细胞均可检测到An-nexinⅡ和uPAR的表达,M3、M4及M5细胞表面AnnexinⅡ和uPAR及其mRNA的表达较高,急性淋巴系白血病(ALL)细胞表面AnnexinⅡ和uPAR及其mRNA的表达极低。结论:急性白血病均存在纤溶激活,纤溶指标异常在急性髓系白血病(主要是M3、M4、M5)更为明显,这与临床上M3、M4、M5患者出血倾向较其他类型AL明显相一致。M3、M4、M5细胞表面AnnexinⅡ和uPAR及其mRNA的表达增高,可能是导致这3种类型白血病纤溶活性增强的因素之一。

Objective：To study the changes of fibrinolysis and leukemic cell expression of Annexin Ⅱ and PAI-1, FDP workinase receptor（uPAR） in patients with various types of acute leukemia（AL）. Method： Plasma fibrinolysis molecular markers were measured by ELISA or chromogenic assay, the Annexin Ⅱ and uPAR on cell surface were measured by flow cytometry, and their mRNA levels in bone marrow mononuclear ceils were detected by RTPCR. Result：The level of PAI-1 ：A and PAI-1 ：Ag in AL patient were higher than normal control, while the activity of plasminogen（PLG） was lower. In addition, the level of FDP in acute myelocytic leukemia （AML） was higher than normal control. Both the highest level of FDP and the lowest activity of PLG were found in acute promyelocytic leukemia（APL）. The expressions of Annexin Ⅱ and uPAR in M3, M4 and M5 were higher compared with other kinds of AL. Conclusion：There were hyperfibrinolysis in AML, especially in M3, M4 and M5, and the expression of Annexin Ⅱ and uPAR were higher too. Abnormal high levels of Annexin Ⅱ and uPAR in leukemia cell may contribute to the production of plasmia, and lead to hyperfibrinolysis.