miR-146a和miR-221在儿童急性T淋巴细胞白血病中的表达及其临床意义

目的:探讨急性T淋巴细胞白血病(T-ALL)患儿外周血单个核细胞(PBMNC)中miR-146a和miR-221表达水平及临床意义。方法:选取海南省第三人民医院收治的初诊T-ALL患儿130例(T-ALL组)和体检健康者50例(对照组)。T-ALL患儿以治疗前作为初发组,诱导治疗d 33达完全缓解者作为缓解组(n=98),未完全缓解者作为难治组(n=32)。采用实时荧光定量PCR方法检测各组PBMNC的miR-146a及miR-221表达水平。ROC曲线分析miR-146a及miR-221对T-ALL的诊断价值,Pearson相关分析评价T-ALL患儿miR-146a及miR-221表达与白细胞计数的相关性。结果:T-ALL组PBMNC的miR-146a及miR-221表达水平均明显高于对照组(5.83±1.54 vs 0.96±0.17)(7.13±2.60 vs 1.64±0.51)(P<0.01)。难治组PBMNC的miR-146a及miR-221表达水平均明显高于缓解组和初发组(8.74±2.35 vs 1.70±0.63,5.83±1.54)(11.316±4.83 vs 2.62±0.85,7.13±2.60)(P<0.01)。miR-146a及miR-221表达水平与白细胞计数、危险度分型和MRD相关(P<0.05)。ROC曲线分析显示,miR-146a及miR-221诊断T-ALL的最佳截值分别为3.90和5.28,2项联合诊断T-ALL的AUC(95%CI)为0.835(0.764-0.892),其敏感度和特异度分别为85.0%和77.2%。相关分析显示,T-ALL患儿PBMNC的miR-146a及miR-221表达水平与白细胞计数均呈正相关(r=0.705,r=0.653,P<0.01),miR-146a与miR-221呈正相关(r=0.784,P<0.01)。结论:miR-146a及miR-221在T-ALL患儿中表达上调,且与T-ALL患儿预后密切相关,2项联合检测对T-ALL诊断具有一定价值。

Expression and Clinical Significance of MiR-146a and MiR-221 in Childhood Acute T Lymphoblastic Leukemia

Objective:To investigate the expression of miR-146 a and miR-211 in peripheral blood mononuclear cells(PBMNC)of children with acute T-lymphoblastic leukemia(T-ALL)and their clinical significance.Methods:One hundred and thirty newly diagnosed children with T-ALL from Hainan Third People′s Hospital(T-ALL group)and50 healthy persons(control group)were selected.The newly diagnosed T-ALL patients before treatment were taken as initial group,the patients reachived complete remission after induction therapy for 33 days were taken as remission group(n=98),the patients not reachived complete remission after induction therapy fore 33 days were taken as rafractory group(n=32).The expression levels of miR-146 a and miR-221 in PBMNC were detected by real-time fluorescence quantitative PCR.ROC curve analysis was used to evaluate the diagnostic value of miR-146 a and miR-221 for T-ALL,Pearson correlation analysis was used to estimate the correlation of miR-146 a and miR-221 expression with white blood cell count in children with T-ALL.Results:The expression levels of miR-146 a and miR-221 of PBMNC in T-ALL group were significantly higher than those in control group(5.83±1.54 vs 0.96±0.17)(7.13±2.60 vs 1.64±0.51)(P<0.01).The expression levels of miR-146 a and miR-221 in refractory group were significantly higher than those in remission group and initial group(8.74±2.35 vs 1.70±0.63 and 5.83±1.54)(11.316±4.83 vs 2.62±0.85 and 7.13±2.60)(P<0.01).The expression levels of miR-146 a and miR-221 correlated with white blood cell count,risk typing and MRD(P<0.05).ROC curve analysis showed that the best cutoff values of miR-146 a and miR-221 for diagnosing childhood T-ALL were 3.90 and 5.28,resoectively.While the AUC(95%CI)of the T-ALL jointy diagnosed by miR-146 a and miR-221 was 0.835(0.764-0.892),and it′s sensitivity and specificity were 85.0%and 77.2%,respectively.The correlation analysis showed that the expression levels of miR-146 a and miR-221 in PBMNC of children with T-ALL positively correlated with the white blood cell count(r=0.705,r=0.653,P<0.01),and that of miR-146 a positively correlated with miR-221(r=0.784,P<0.01).Conclusion:The expression of miR-146 a and miR-221 is up-regulated in children with T-ALL and closely relates with the prognosis of children with T-ALL.The combined detection of miR-146 a and miR-221 is certain value for diagnosis of T-ALL.