Expression and function of the FAS antigen in B chronic lymphocytic leukemia and hairy cell leukemia.
Expression and function of the FAS antigen in B chronic lymphocytic leukemia and hairy cell leukemia.
复制标题
FAS抗原在B型慢性淋巴细胞白血病和毛细胞白血病中的表达和功能。
作者：
P. Panayiotidis;K. Ganeshaguru;L. Foroni;A. Hoffbrand
应用特异性IgM单抗和流式细胞仪分析了21例慢性B淋巴细胞白血病(CLL)和4例毛细胞白血病(HCL)患者Fas抗原的表达和功能。在21例CLL患者中，有10例(5-41%，平均15.6%)的CLL细胞表达Fas抗原，在自发或氢化可的松诱导的CLL细胞凋亡过程中，Fas抗原的表达没有改变。相反，加入干扰素可上调所有CLL患者Fas的表达，体外培养2天后，65-100%(平均84.8%)的细胞呈阳性。19例慢性淋巴细胞性白血病患者经α-干扰素培养后15例Fas表达，培养2天后15-74%(平均34%)为Fas+细胞。IL-4和IL-10分别抑制和促进CLL的凋亡，但不改变Fas的表达。流式细胞仪分析结果与半定量逆转录聚合酶链式反应(RT-PCR)分析新鲜和培养CLL细胞Fas基因的结果一致。虽然IL-4和IFN在体外可以阻止CLL细胞的凋亡，但目前的结果表明，IFN诱导了凋亡诱导蛋白Fas的表达。抗Fas单抗对Fas+CLL细胞无杀伤作用(对Fas+Jurkat和4株淋巴母细胞系有杀伤作用)。这种耐药性不是由于突变的Fas蛋白造成的，因为在三名CLL患者的白血病细胞中只发现了野生型Fas基因。在4例HCL患者中，34-53%(平均44.5%)的白血病细胞为Fas+，且对抗Fas介导的细胞毒作用也有抵抗。高bcl2蛋白水平和对抗Fas介导的细胞毒作用的抵抗可能是延长CLL和HCL细胞在体内存活的原因之一。
The expression and function of the FAS antigen was analyzed in 21 patients with B chronic lymphocytic leukemia (CLL) and four with hairy cell leukemia (HCL) using a specific IgM monoclonal antibody and FACS analysis. The FAS antigen was expressed in a minority (5-41%, mean 15.6%) of the CLL cells in 10 of 21 CLL patients and this expression was not modified during spontaneous or hydrocortisone-induced apoptosis of CLL cells. In contrast, culture with gamma-interferon (gamma-IFN) upregulated the expression of FAS in all CLL patients, with 65-100% (mean 84.8%) of the cells being positive after 2 days in vitro culture. Culture with alpha-IFN induced FAS expression in 15 of 19 CLL patients tested, with 15-74% (mean 34%) of the cells being FAS+ after 2 days culture. IL-4 and IL-10, lymphokines that inhibit and promote CLL apoptosis respectively, did not modify the expression of FAS. These results from FACS analysis were consistent with FAS mRNA analysis of fresh and cultured CLL cells, using a semi-quantitative reverse transcriptase (RT)-PCR technique. Although IL-4 and IFNs prevent apoptotic cell death of CLL cells in vitro, the present results show that IFNs induce the expression of the apoptosis-inducing protein FAS. However, FAS+ CLL cells were not killed in the presence of anti-FAS monoclonal antibody (while the FAS+ Jurkat and four lymphoblastoid cell lines were killed). This resistance is not due to a mutated FAS protein, since only wild-type FAS cDNA was demonstrated in the leukemic cells of three CLL patients. In four HCL patients 34-53% (mean 44.5%) of the leukemic cells were FAS+ and they were also resistant to the anti-FAS mediated cytotoxicity. The combination of high bcl-2 protein levels and resistance to anti-FAS mediated cytotoxicity may contribute to the extended in vivo survival of CLL and HCL cells.