Zhang R, Yang J Y, Sun H Q, Jia H, Liao J, Shi Y J, Li G
Department of Pediatrics Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan Province, China.
Eur Rev Med Pharmacol Sci. 2015;19(14):2679-88.
Wilms tumor gene 1 (WT1) has been identified as an independent risk prognostic factor in acute leukemia. However, there exists a controversy that WT1 as a marker for minimal residual disease (MRD) monitoring in acute leukemias. We detected WT1-RNA transcript level to estimate the diagnostic value of monitoring MRD in childhood acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
WT1 mRNA expression levels were detected by real-time quantitative reverse transcriptase PCR (qRT-PCR) in bone marrow (BM) samples from 107 childhood ALL and 35 childhood AML at diagnosis. MRD was consecutively performed after induction and consolidation (early intensification in ALL) chemotherapy. Receiver operating characteristics (ROC) analysis and the largest areas under the curve (AUC) were applied to define optimal threshold value of MRD level. Sensitivity, specificity, positive likelihood ratio (+LR) and negative likelihood ratio (-LR) were used to evaluate diagnostic power for MRD. Relapse free survival (RFS) was evaluated by the Kaplan-Meier statistical method.
The largest areas under the curve (AUC), specificity, +LR and -LR showed higher accuracy in childhood AML than ALL. Compared the diagnostic parameters, the post-induction time wasn't good enough to show the better time than post-consolidation time for MRD assessment in AML. The threshold was set at 150 WT1 copies/104 ABL copies as the optimal cut-off value of MRD level post induction in childhood AML. MRD+ (WT1>150) children had increased the risk of relapse with poor prognosis, showing lower RFS than MRD- group (p=0.01). However, the threshold 70 WT1 copies/104 ABL copies post induction in childhood ALL did not show clinical significance for predicting prognosis (p=0.056).
WT1 gene will be a useful marker for monitoring MRD to predict relapse in childhood AML. But it did not show good enough to monitor MRD in childhood ALL.
威尔姆斯瘤基因1（WT1）已被确定为急性白血病的独立风险预后因素。然而，WT1作为急性白血病微小残留病（MRD）监测标志物存在争议。我们检测WT1-RNA转录水平，以评估监测MRD在儿童急性髓系白血病（AML）和急性淋巴细胞白血病（ALL）中的诊断价值。
采用实时定量逆转录聚合酶链反应（qRT-PCR）检测107例儿童ALL和35例儿童AML诊断时骨髓（BM）样本中WT1 mRNA表达水平。诱导和巩固（ALL为早期强化）化疗后连续进行MRD检测。应用受试者工作特征（ROC）分析和最大曲线下面积（AUC）确定MRD水平的最佳阈值。采用敏感性、特异性、阳性似然比（+LR）和阴性似然比（-LR）评估MRD的诊断效能。采用Kaplan-Meier统计方法评估无复发生存期（RFS）。
曲线下最大面积（AUC）、特异性、+LR和-LR在儿童AML中显示出比ALL更高的准确性。比较诊断参数，诱导后时间在AML的MRD评估中不足以显示比巩固后时间更好的时间。阈值设定为150个WT1拷贝/104个ABL拷贝，作为儿童AML诱导后MRD水平的最佳截断值。MRD+（WT1>150）儿童复发风险增加，预后不良，RFS低于MRD-组（p=0.01）。然而，儿童ALL诱导后阈值70个WT1拷贝/104个ABL拷贝对预测预后无临床意义（p=0.056）。
WT1基因将是监测MRD以预测儿童AML复发的有用标志物。但它在监测儿童ALL的MRD方面表现不够好。
