Id4基因甲基化检测在儿童恶性淋巴瘤中的意义  

Detection of malignant lymphoma in children by using Id4 gene methylation indicator

作　　者：刁玉巧[1] 曲凡[1] 杨明娟[2] 朱秀丽[1] 李梅[1] 

机构地区：[1]河北医科大学第四医院儿科,石家庄050011 [2]昌邑市人民医院儿科

出　　处：《中华实用儿科临床杂志》2013年第3期195-198,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：河北省卫生厅医学科学研究重点课题计划（08347）

摘　　要：目的检测恶性淋巴瘤Ⅳ期患儿骨髓Id4基因甲基化情况，以探讨其在淋巴瘤发生、发展中的作用。方法将42例确诊为恶性淋巴瘤Ⅳ期[包括霍奇金病（HD），非霍奇金淋巴瘤（NHL）]患儿治疗前、化疗前期、化疗中期、化疗后期、临床缓解以及复发病例的骨髓标本作为研究组，非血液肿瘤患儿20例骨髓作为对照组。采用甲基化特异性聚合酶链反应（MS-PCR），分别检测研究组与对照组患儿骨髓细胞中Id4基因的甲基化状态，RT-PCR检测研究组与对照组Id4基因mRNA的表达情况。结果MS—PCR检测结果：治疗前27例出现完全性和部分甲基化条带，甲基化阳性率为64．3％（27／42例）。对照组均呈非甲基化状态，2组比较差异有统计学意义（P〈0．001）。动态观察研究组27例（NHL21例，HD6例），NHL化疗前期15例出现ld4基因甲基化条带，阳性率为55．6％（15／27例）；化疗中期阳性率51．9％（14／27例）；化疗后期阳性率48．1％（13／27例）；临床缓解9例，有4例检出，阳性率为44．4％（4／9例）。复发2例，甲基化状态消失后又重新出现。治疗前与化疗前、化疗中期比较差异均无统计学意义（P均〉0．05），与化疗后期比较，差异有统计学意义（P〈0．05）。不同分型间甲基化阳性率比较差异均无统计学意义（P均〉0．05）。RT-PCR检测结果：研究组治疗前，凡有Id4基因甲基化病例均无mRNA表达，对照组全部有表达。结论在儿童恶性淋巴瘤Id4基因呈特异性高甲基化状态导致该基因表达沉默，这与淋巴瘤的发生、发展及转归密切相关。随着化疗病情的变化，Id4基因高甲基化状态也随之变化。因此，Id4基因甲基化状态有可能作为恶性淋巴瘤患儿早期发现、疗效判断和微小残留检测的指标。Objective To study and discuss what part does methylated IdA gene participate in malignant lymphoma stage tV by detecting the extent of how much Id4 gene has been methylated in afflicted children who suffer from malignant lymphoma. Methods Forty-two patients who had diagnosed with malignant lymphoma [ Hodgkin＇s disease （HD） ,Non-Hodgkin＇s lymphoma（NHL） ] were selected as study group. Their chemotherapy stages of pre-treatment, early-treatment ,mid-treatment, post-treatment and clinical remissions or relapse throughout the entire treatment had been traced. At each stage the expression of methylated IdA gene mRNA was detected by methylation-specific polymerase chain reaction （MS-PCR） and compared with the control group. The control group consisted of 20 non-neoplastic hematologic disorder affected children as sample donors. Results MS-PCR detection：in pre-treatment stage,there were 27 patients who were found methylated or partially methylated IdA genes. Methylated ratio was thus at 64.3% （27 pa- tients out of a total of 42 patients）. Those 27 patients were actively traced down along with different stages of treatment （21 NHL patients,6 HD patients）. Before NHL there was 55.6% methylated IdA gene （15 cases out of 27 NHL patients）. During chemotherapy treatment, there was 51.9% of methylated IdA gene positive （ 14 cases out of 27 patients）. In post chemotherapy treatment, there was 48.1% of methylated IdA gene positive （ 13 cases out of 27 patients）. Totally there were 9 patients showed clinical recovery after chemotherapy. There was 44.4% of traceable methylated IdA gene after recovered chemotherapy patients （4 recovered patients still carrying positive reading of methylated IdA gene out of totally 9 recovered patients）. There were 2 patients relapsed, with traceable methylated IdA gene re-appeared in them afterwards. Throughout different treatment stages, there was no significant correlation in the treatment re- sult and the appearance of methylated IdA gene in early treatm

关 键 词：恶性淋巴瘤 甲基化 ID4基因 儿童 

分 类 号：R733.1[医药卫生—肿瘤]