表观遗传学调控急性B淋巴白血病细胞系表面脊髓灰质炎病毒受体表达  

Poliovirus Receptor on Surface of Acute B Lymphoid Leukemia Cells Modulated by Epigenetic Mechanism

作　　者：王蔚[1,2] 高丽[1] 王新荣[1] 康慧媛[1] 李永辉[1] 于力[1] 

机构地区：[1]中国人民解放军总医院血液科,北京100853 [2]卫生部中日友好医院血液科,北京100029

出　　处：《中国实验血液学杂志》2011年第6期1357-1361,共5页Journal of Experimental Hematology

基　　金："国家自然科学基金"(编号0919044及30971297);"北京首发基金"(编号2007-2040);"国家973计划"(编号2005CB522400)资助

摘　　要：本研究探讨急性B淋巴白血病细胞表面脊髓灰质炎病毒受体表达是否受表观遗传学调控。利用重硫酸盐PCR测序方法比较去甲基化药物5-氮杂胞苷作用前后,急性B淋巴白血病细胞系RS4:11和SUP-B15中脊髓灰质炎病毒受体基因启动子区甲基化CpG百分比的变化,利用流式细胞分析技术和实时定量PCR技术在转录和翻译水平比较该基因表达的变化;比较组蛋白去乙酰化酶抑制剂作用前后,该基因在转录和翻译水平表达的变化。结果显示:急性B淋巴白血病细胞系RS4:11和SUP-B15中脊髓灰质炎病毒受体基因启动子区存在异常高甲基化的CpG岛,经去甲基化药物作用后甲基化CpG含量减低,而且该基因在转录及蛋白水平的表达也相应增加。经过组蛋白脱乙酰酶抑制剂作用后,该基因在转录和蛋白水平的表达也相应增加。上述两种药物合用与单药作用相比,并未进一步提高该基因在转录和蛋白水平的表达,提示异常甲基化和组蛋白去乙酰化这2种表观遗传学调控机制在抑制脊髓灰质炎病毒受体表达方面没有协同作用。结论:急性B淋巴白血病细胞系表面脊髓灰质炎病毒受体表达受表观遗传学调控,药物处理后能部分逆转异常的表观遗传学调节机制,使得该基因的表达部分恢复。The aim of this study was to identify if the expression of poliovirus receptor（PVR） on the surface of acute B lymphoid leukemia（B-ALL） cells RS4：11 and SUP-B15 is modulated by epigenetic mechanism.B-ALL cell lines RS4：11 and SUP-B15 were treated with demethylation agent.Bisulfite PCR was performed to detect percentage change of the methylated CpG islands in the promoter region of PVR.In the meantime,the expression levels of PVR at the translation and transcription levels were detected by flow cytometry and RT-PCR respectively.The B-ALL cell lines were also treated with histone deacetylase（HDAC） inhibitor.The expression level of the gene mRNA and protein was detected too.The results indicated that after treated with 5-azacytidine,the hypermethylated status of PVR promoter region was partly reversed,and the expression of PVR at both mRNA and protein levels was restored in the meanwhile.HDAC inhibitor suberoylanilide hydroxamic acid could also increase the PVR expression.But there was no synergistic function between hypermethylation and HDAC as for repressing PVR transcription in B-ALL cell lines.It is concluded that the expression of PVR in B-ALL cells is modulated by epigenetic mechanisms.Treatment with corresponding inhibitors can partly restore the gene′s expression in both mRNA and protein levels.

关 键 词：急性B淋巴细胞白血病 表观遗传学 脊髓灰质炎病毒受体 

分 类 号：R733.71[医药卫生—肿瘤]