摘要
为了探讨IL 6R的α亚单位基因与蛋白在人白血病细胞中的表达 ,为临床利用IL 6 /IL 6R系统介导重组IL 6 PE4 0外毒素融合蛋白靶向杀伤白血病细胞提供可靠依据 ,采用RT PCR半定量技术、直接免疫荧光标记及流式细胞术检测了IL 6R的α亚单位基因及蛋白在多种人白血病细胞细胞系中的表达。结果表明 ,粒系、单核系、红白血病细胞系HL 6 0 ,KG 1,U937和TF 1均高表达IL 6R的α亚单位基因和蛋白 ;淋巴系白血病细胞系Raji亦有一定量的基因表达 ;而淋巴系细胞等CEM和HuT2 8以及慢性粒细胞白血病细胞系K5 6 2无论是IL 6Rα亚单位的基因还是蛋白均为阴性。相对表达丰度依次为KG 1>TF 1>U2 6 6 >U937>HL 6 0 >Raji。鉴于粒系、单核系、红白血病细胞高表达IL 6Rα亚单位的基因和蛋白 ,而IL 6Rα亚单位蛋白在正常人外周血细胞均为阴性表达这一事实 ,提示可以利用IL 6 /IL 6R系统介导重组IL 6 PE4 0外毒素融合蛋白进行靶向杀伤和治疗这些白血病 。
To probe into the expression of α subunit for IL 6R at both mRNA and protein levels in human leukemic cells and to discuss its implication in targeted treatment for leukemia with recombinant IL 6 PE40 exotoxin fusion protein mediated by IL 6/IL 6R system, semi quantitative RT PCR, sequencing and FCM were used to analyse the gene and protein expression levels of α subunit for IL 6R in leukemic cells. Our results showed that not only mRNA but also protein of α subunit for IL 6R are highly expressed in the myelogenous leukemic cell lines, the relative expression levels of mRNA were KG 1(1.22)>TF 1(1.02)>U266(1.00)>U937(0.99)>HL 60(0.76). Among lymphoblastic leukemic cell lines, Raji expressed a certain amount of α subunit mRNA (0.77), whereas its α subunit protein was not detected. Expression of α subunit mRNA and protein were negative in lymphoblastic leukemic cell lines, HuT28 and CEM, and chronic myelocytic leukemic cell line K562. These results correlate with those of FCM highly. Noteworthily, normal human peripheral blood mononuclear cells expressed hardly protein of IL 6R α subunit. So this study provides sufficient experimental evidence that the targeted treatment by recombinant IL 6 PE40 can specifically kill leukemic cells highly expressing IL 6R without toxicity to normal hematopoietic cells.
出处
《中国实验血液学杂志》
CAS
CSCD
2002年第1期22-26,共5页
Journal of Experimental Hematology
基金
国家自然科学基金资助项目 编号 3950 0 0 62和 39870 875