SOCS3基因甲基化状态与儿童急性淋巴细胞白血病治疗反应及预后的相关性  

Correlations of SOCS3 methylation status with treatment outcome and prognosis of children with acute lymphoblastic leukemia

作　　者：江傲霜 王宁玲[1] 刘亢亢[1] 吴正玉 储金华[1] 杨林海[1] Jiang Aoshuang;Wang Ningling;Liu Kangkang(Dept of Pediatrics,The Second Affiliated Hospital of Anhui Medical University,Hefei 230601)

机构地区：[1]安徽医科大学第二附属医院儿科,合肥230601

出　　处：《安徽医科大学学报》2020年第5期795-799,803,共6页Acta Universitatis Medicinalis Anhui

基　　金：安徽省卫生和计划生育委员会科研项目(编号:13FR026);安徽医科大学2016-2017年度校科研基金(编号:2017xkj035);安徽医科大学第二附属医院“火花计划”科研项目(编号:2015hhjh09)。

摘　　要：目的研究儿童急性淋巴细胞白血病(ALL)中细胞因子信号转导抑制因子3(SOCS3)的DNA甲基化水平,探讨其与儿童ALL治疗反应与预后的相关性。方法收集83例入组ALL患儿及21例健康儿童(健康对照组)骨髓标本,分别采用逆转录定量聚合酶链式反应(qRT-PCR)和甲基化特异性PCR技术对ALL初诊组、完全缓解组、复发组及正常儿童骨髓单个核细胞中SOCS3 mRNA表达水平和SOCS3基因甲基化水平进行检测,采用SPSS 17.0软件进行统计分析,分析SOCS3mRNA表达水平和SOCS3基因甲基化水平之间的关系、SOCS3基因甲基化水平与ALL患儿治疗反应的关系;并采用Kaplan-Meier法绘制生存曲线,比较SOCS3甲基化状态与累积复发率(CIR)和总生存率(OS)的相关性。结果①ALL患儿初诊组、复发组SOCS3 mRNA的表达水平明显低于健康对照组儿童SOCS3 mRNA的表达水平(P<0.05),完全缓解组患儿SOCS3 mRNA的表达水平基本恢复正常;②初诊组、复发组、完全缓解组ALL患儿的SOCS3基因甲基化水平明显高于健康对照组(P<0.05);初诊组及复发组ALL患儿的SOCS3基因甲基化水平明显高于完全缓解组(P<0.05);③运用中位数方法将ALL患儿SOCS3基因甲基化水平分为高水平和低水平组,42个月随访结果显示SOCS3甲基化高水平组CIR明显高于低表达水平组(P<0.05),但两组的OS比较差异无统计学意义(P>0.05)。结论SOCS3基因甲基化导致SOCS3的低表达,监测SOCS3甲基化水平可有助于了解儿童ALL的治疗反应及预后,通过去甲基化调节SOCS3 mRNA的表达可能成为儿童ALL靶向治疗的新方向。Objective To investigate the promoter methylation level of the cytokine signaling 3(SOCS3)in children with acute lymphoblastic leukemia(ALL),and to explore its correlation with the treatment outcome and prognosis for ALL children.Methods The SOCS3 mRNA and methylation levels in bone marrow mononuclear cells were detected in 83 cases of newly diagnosed ALL at initial diagnosis,completely remission,relapse and 21 healthy control children through reverse transcription quantitative polymerase chain reaction(qRT-PCR)and methylationspecific PCR,respectively.SPSS 17.0 software was employed for statistical analysis to analyze the relationship between the level of SOCS3 mRNA expression and the methylation level of SOCS3 gene,the relationship between the methylation level of SOCS3 and the treatment outcome of the children with ALL.Meanwhile,The methylation level of SOCS3 gene in children with ALL was classified into high or low level group by the median method.The correlations of SOCS3 methylation status with the cumulative incidence of relapse rate(CIR)and overall survival rate(OS)were compared.Results The SOCS3 mRNA expression levels in initial diagnosis group and relapse group were remarkably lower than that in healthy control group(P<0.05).The methylation level of SOCS3 in ALL children was evidently higher than that in healthy control group(P<0.05).The results of 42 months follow-up showed that the CIR in high level group was dramatically higher than that in low level group(P<0.05),but there was no significant difference in the OS between these two groups(P>0.05).Conclusion SOCS3 methylation leads to low expression of SOCS3,and monitoring the SOCS3 methylation level can help to understand the treatment outcome and prognosis for ALL children.

关 键 词：儿童 急性淋巴细胞白血病 细胞因子信号转导抑制因子-3 甲基化 治疗反应 预后 

分 类 号：R725.5[医药卫生—儿科]