肾母细胞瘤1基因表达及其对急性髓系白血病患者预后的预测价值

Expression of WT1 gene and its prognostic value in patients with acute myeloid leukemia

目的:分析急性髓系白血病(AML)患者肾母细胞瘤1(WT1)基因表达水平的差异,探讨WT1表达及其在核仁磷酸蛋白1(NPM1)或Fms样酪氨酸激酶3内部串联重复(FLT3-ITD)不同突变状态下与AML患者疗效和生存的相关性,评估其对于患者预后的预测价值。方法:以167例初发AML患者(除外M3亚型)为研究对象,根据初诊时WT1表达水平分为WT1高表达组和WT1低表达组,回顾性分析两组的临床及实验室检查资料,采用Kaplan-Meier法进行患者生存分析以明确WT1表达水平在预后评估中的价值,特别是在NPM1或FLT3-ITD不同突变状态AML患者中的预后评估价值。结果:WT1高表达组126例患者中治疗有效83例(65.9%),低表达组41例患者中治疗有效39例(95.1%),差异有统计学意义(P<0.01)。WT1高表达组2年总存活率低于WT1低表达组(46.1%和75.2%,P<0.05),2年无病存活率也低于WT1低表达组(43.5%和68.5%,P<0.05)。诱导化疗前后WT1表达量下降≥1 log患者总反应率和2年总存活率优于下降<1 log患者(均P<0.05),但两者2年无病存活率差异无统计学意义(P>0.05)。NPM1野生型患者中,WT1高表达组总反应率、2年总存活率较WT1低表达组低(均P<0.05);FLT3-ITD野生型患者中,WT1高表达组总反应率、2年总存活率和2年无病存活率均较WT1低表达组低(均P<0.05);而NPM1或FLT3-ITD突变患者中,不同WT1表达水平组疗效及生存分析结果差异无统计学意义(均P>0.05)。结论:初发AML患者中WT1基因过表达提示预后不良;诱导治疗后WT1表达量下降≥1 log的患者预后优于下降<1 log的患者;初诊WT1基因表达水平可以作为NPM1或FLT3-ITD野生型AML患者的预后判断指标。

Objective:To investigate the expression of Wilms’tumor 1(WT1)gene in patients with acute myeloid leukemia(AML),and to explore its application in predicting prognosis of AML in patients with wild or mutated nucleophosmin 1(NPM1)and Fms-like tyrosine kinase 3-internal tandem duplication(FLT3-ITD).Methods:One hundred and sixty-seven newly diagnosed AML patients(exclued M3 type)were enrolled in this study.The survival of patients were analyzed with Kaplan-Meier method.The clinical data,laboratory findings and the survival of patients were analyzed and compared between patients with high WT1 expression(high-WT1 group)and those with low WT1 expression(low-WT1 group),as well as among the patients with NPM1 or FLT3-ITD wild type and mutants.Results:The overall response rates(ORR)in high-WT1 and low-WT1 groups were 65.9%(83/126)and 95.1%(39/41),respectively(P<0.01).Compared with the low-WT1 group,the high-WT1 group had lower 2-y overall survival(OS)rate(46.1%vs.75.2%,P<0.05)and 2-y disease free survival(DFS)rate(43.5%vs.68.5%,P<0.05).After induction chemotherapy,the patients with decreased WT1 gene expression≥1log was associated with higher ORR and 2-y OS rate(all P<0.05),but the advantage of 2-y DFS rate was not shown(P>0.05).In patients with NPM1 wild type,the high-WT1 group had inferior ORR and 2-y OS rate(all P<0.05),while in the patients with FLT3-ITD wild type,the high-WT1 group had inferior ORR,2-y OS rate and 2-y DFS rate(all P<0.05).In patients with NPM1 or FLT3-ITD mutations,the WT1 expression had no significantly predicting values in treatment efficacy and survival(all P>0.05).Conclusions:WT1 gene overexpression indicated poor prognosis of AML patients;the patients with decreased WT1 gene expression≥1 log after the first induction therapy show better prognosis than those with<1 log.The WT1 gene expression level at diagnosis can be used as an unfavorable prognostic factor for AML patients with NPM1 or FLT3-ITD wild types.