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目的 探讨全反式维甲酸 (ATRA)和三氧化二砷 (As2 O3)在体内外对急性早幼粒细胞性白血病 (APL)细胞组织因子 (TF)表达的影响。方法 利用复钙时间测定、ELISA和RT PCR等方法 ,分别检测了ATRA和As2 O3 治疗前后APL患者骨髓单个核细胞的促凝活性、TF抗原及其mRNA的转录水平 ,同时还检测了使用ATRA和As2 O3 处理APL细胞株NB4细胞和NB4 R1细胞以及转染PML RARa融合基因的U937细胞的促凝活性、TF抗原及其mRNA的转录水平。结果 ATRA和As2 O3 在体内和体外均可以时间依赖的方式下调NB4细胞的促凝活性、TF抗原水平以及TFmRNA的转录。转染PML RARa融合基因的U937细胞与仅转染逆病毒载体的U937细胞相比 ,其TF表达水平显著升高 ;使用ATRA或As2 O3 分别处理转染PML RARa和转染逆病毒载体的U937细胞 ,其TF抗原水平均显著降低。结论 ATRA和As2 O3均可下调APL细胞TF的表达并降低其PCA ,As2 O3在诱导APL细胞凋亡的同时有可能通过下调APL细胞TF的表达而改善APL患者与DIC相关的出血症状。结果还提示APL细胞染色体易位产生的融合蛋白PML RARa可能对TF的异常表达有一定的影响 ,而ATRA和As2 O3对TF的下调作用可能不依赖于对融合蛋白PML RARa的降解。
Objective To investigate the effects of all-trans retinoic acid (ATRA) and As 2 O 3 on the expression of tissue factor (TF) in acute promyelocytic leukemia (APL) cells in vitro and in vivo. Methods The procoagulant activity, TF antigen and mRNA transcription of bone marrow mononuclear cells in APL patients before and after treatment with ATRA and As 2 O 3 were detected by calcium counter-current assay, ELISA and RT-PCR respectively. ATRA and Proliferation, TF antigen and mRNA transcription of APL cell line NB4 cells and NB4 R1 cells as well as U937 cells transfected with PML RARa fusion gene were treated with As2 O3. Results Both ATRA and As2 O3 down-regulated the procoagulant activity, the level of TF antigen and the transcription of TF mRNA in NB4 cells in a time-dependent manner in vivo and in vitro. U937 cells transfected with the PML RARa fusion gene showed significantly increased TF expression compared with U937 cells transfected with the retroviral vector alone. U937 cells transfected with PML RARa and retroviral vectors were treated with ATRA or As 2 O 3, respectively , Its TF antigen levels were significantly lower. Conclusions Both ATRA and As2 O3 can down-regulate the expression of TF in APL cells and reduce the apoptosis of APL cells induced by As2 O3, and at the same time, it is possible to improve the DIC-related hemorrhagic symptoms in APL patients by down-regulating the expression of TF in APL cells. The results also suggest that PML RARa, a fusion protein produced by the chromosomal translocation of APL cells, may have an influence on the abnormal expression of TF. The down-regulation of TF by ATRA and As2 O3 may not depend on the degradation of the fusion protein PML RARa.