Liu Yan-Hui, Wang Zhao-Yue, Zhang Wei, Dai Lan, Shen Wen-Hong, Ruan Chang-Geng
First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou 215006, China.
Zhonghua Xue Ye Xue Za Zhi. 2009 Mar;30(3):145-9.
To study the fibrinolytic activity in patients with acute promyelocytic leukemia (APL) and its alteration in all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) treatment.
Plasma fibrinogen concentration was determined with the conventional method, and the levels of fibrin degradation products (FDP) and D-dimer were quantified with ELISA. Plasminogen was measured by chromogenic assay. Cell surface expression of Annexin II and u-PAR and their mRNA levels were measured by flow cytometry and real time-PCR, respectively.
The levels of FDP and D-dimer in APL were remarkably higher in APL patients than that in normal controls, while fibrinogen and plasminogen were lower. Both Annexin II and u-PAR were highly expressed on APL cells, which declined after treatment with ATRA and/or ATO, but remained higher than those on normal bone marrow mononuclear cells.
Abnormally high levels of Annexin II and u-PAR expression on APL cells may contribute to the increased production of plasmin, leading to primary hyperfibrinolysis in APL. ATRA and ATO therapy induces down-regulation of Annexin II and u-PAR expression, which may be contribute, at least in part, to the relief of the hemorrhagic complications in APL.
研究急性早幼粒细胞白血病(APL)患者的纤溶活性及其在全反式维甲酸(ATRA)和/或三氧化二砷(ATO)治疗中的变化。
采用常规方法测定血浆纤维蛋白原浓度,用ELISA法测定纤维蛋白降解产物(FDP)和D - 二聚体水平。用发色底物法测定纤溶酶原。分别用流式细胞术和实时定量PCR检测膜联蛋白II和尿激酶型纤溶酶原激活物受体(u - PAR)的细胞表面表达及其mRNA水平。
APL患者FDP和D - 二聚体水平显著高于正常对照,而纤维蛋白原和纤溶酶原水平较低。APL细胞上膜联蛋白II和u - PAR均高表达,经ATRA和/或ATO治疗后下降,但仍高于正常骨髓单个核细胞。
APL细胞上膜联蛋白II和u - PAR表达异常增高可能导致纤溶酶生成增加,引起APL原发性纤溶亢进。ATRA和ATO治疗诱导膜联蛋白II和u - PAR表达下调,这可能至少部分有助于缓解APL的出血并发症。