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人急性白血病细胞中Fas(CD95)的表达及其功能
QUALITATIVE AND QUANTITATIVE CHARACTERIZATION OF FAS(CD95) EXPRESSION AND ITS ROLEIN PRIMARY HUMAN ACUTE LEUKEMIA CELLS
【摘要】 目的:研究急性白血病细胞中Fas的定性和定量表达及功能。方法:应用流式细胞术及RT蛳PCR方法检测急性白血病患者外周血或骨髓中白血病细胞的Fas定性和定量表达,并用Annexin V染色法检测其功能。结果:急性白血病细胞中Fas蛋白呈单峰状表达,具有不同的密度,并且在不同类型细胞中表现出不同的定量特征;Fas呈定性阴性或定量弱表达的患者中,其全长和剪接体mRNA的表达水平与蛋白的表达水平有关;新分离出来的白血病细胞在体外与pokeweed(PWA)抗原共同培养后,可引起Fas表达水平的上调;新鲜的急性淋巴细胞白血病(ALL)和急性髓系白血病(AML)细胞对于抗Fas IgM抗体有抵抗能力,而鬼臼乙叉苷(etoposide, ETP)能够引起所有类型的急性白血病细胞产生凋亡。抗Fas IgM抗体和ETP的联合使用并不能产生协同效果。结论:Fas是ALL和AML细胞的一个生物学标志,该研究为探讨细胞毒素制剂和细胞因子治疗作用的机制提供了线索。
【Abstract】 Objective:Acute leukemia cells were studied qualitatively and quantitatively for the expression of Fas as well as its function.Methods:Blood or bone marrow samples from patients with acute leukemia were examined qualitatively and quantitatively for the expression of Fas as well as its function using flow cytometry RTPCR and the annexin V staining method.Results:Fas expressin was flow cytometrically unimodal with heterogeneous density,and showed quantitatively characteristic features in different diseases.Both the fulllength and the alternatively spliced truncated mRNAs were detected constitutively even in acute leukemia cells with qualitatively negative and quantitatively faint Fas,their level of expression were correlated with the level of expression of Fas protein.Shortterm culturing of freshly isolated leukemia cells with pokeweek antigen gave rise to an increase of Fas density.The fresh ALL and AML cellswere resistant to the antiFas IgM antibody,while etoposide could trigger apoptosis in all types of leudemia tested.The combined effects of the antiFas MoAb and etoposide were not always synergistic.Conclusion:Fas is a biological marker for characterizing ALL and AML cells,and provide insight into creating a new therapeutic modality using cytotoxic agents and cytokines together with modulation of Fas.
【Key words】 Fas(CD95 ); Apoptosis; Acute leukemia; Flow cytometry;
- 【文献出处】 白血病.淋巴瘤 ,Journal of Leukemia & Lymphoma , 编辑部邮箱 ,2004年01期
- 【分类号】R733.71
- 【下载频次】72