中文摘要：

目的探讨细胞毒性T淋巴细胞相关抗原-4（cytotoxic T lymphocyte antigen-4,CTLA-4）在儿童急性淋巴细胞性白血病（acute lymphoblastic leukemia,ALL）细胞中的表达情况,并进一步研究CTLA-4对ALL细胞增殖、凋亡等方面的影响。方法以儿童ALL Nalm-6、Jurkat细胞为模型,探讨CTLA-4在ALL细胞的表达情况。并将Nalm-6、Jurkat细胞与CTLA-4抑制剂共培养,收集细胞,提取蛋白质及mRNA,行CCK-8、Western blot分析、实时定量PCR分析,研究CTLA-4对ALL细胞增殖、凋亡的影响。结果 Western blot检测发现ALL细胞表达CTLA-4。经CTLA-4抑制剂处理后,Jurkat细胞的凋亡蛋白Bax、Caspase-3表达量明显增加,Nalm-6细胞凋亡蛋白Caspase-3表达量明显增加;2种细胞抗凋亡蛋白Bcl-2表达量均明显下降;2种细胞ALDH1A1、ALDH1A3、ALDH2mRNA表达量均明显下降。结论儿童ALL细胞表达CTLA-4分子,CTLA-4抑制剂可以抑制儿童ALL细胞增殖,诱导细胞凋亡,抑制ALDH＋的干细胞样肿瘤细胞的生长。抑制CTLA-4有望成为ALL治疗的新方向。

英文摘要：

Objective To investigate the expression of cytotoxic T lymphocyte antigen-4（CTLA-4）in childhood acute lym-phoblastic leukemia（ALL）cells and the effect of the CTLA-4 inhibitor on the proliferation and apoptosis of childhood ALL cells.Methods The expression of CTLA-4 was detected in ALL cells with ALL Nalm-6 and Jurkat cells as cell model.Nalm-6 and Jurkat cells were co-cultured with the CTLA-4 inhibitor and subjected to extraction of protein and mRNA.The effect of CTLA-4 on the proliferation and apoptosis of ALL cells was examined by CCK-8,Western blotting and real-time quantitative PCR,respectively.Results Western blotting showed that CTLA-4 expressed in ALL cells.The expression levels of Bax and Caspase-3 were significantly increased in Jurkat cells and those of Caspase-3 obviously elevated in Nalm-6 cells after treatment with the CTLA-4 inhibitor.The expression levels of Bcl-2 were found to profoundly decrease in both cells treated with the CT-LA-4 inhibitor.The expression levels of ALDH1A1,ALDH1A3,and ALDH2 mRNA were markedly down-regulated after treatment with the CTLA-4 inhibitor.Conclusion CTLA-4 was expressed in ALL cells.As the CTLA-4 inhibitor can inhibit the proliferation of ALL cells,induce their apoptosis and suppress the growth ALDH＋ stem cell-like tumor cells,CTLA-4 may become a new treatment target of ALL.