肾母细胞瘤1基因联合多参数流式细胞术检测微小残留病灶评估急性髓系白血病患儿预后的价值  

Value of Wilms tumor 1 gene combined with multiparameter flow cytometry for minimal residual disease in evaluating prognosis of children with acute myeloid leukemia

作　　者：史利欢 陈静[1] 谢昕 范朋凯 刘炜[1] SHI Lihuan;CHEN Jing;XIE Xin;FAN Pengkai;LIU Wei(Key Laboratory of Pediatric Hematology Medicine of Henan Province,the Children′s Hospital Affiliated to Zhengzhou University,Henan Provincial Children′s Hospital,Zhengzhou,Henan,450018)

机构地区：[1]郑州大学附属儿童医院/河南省儿童医院、河南省小儿血液医学重点实验室,河南郑州450018

出　　处：《实用临床医药杂志》2023年第24期82-88,92,共8页Journal of Clinical Medicine in Practice

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20210627);河南省科技攻关项目(232102310048)。

摘　　要：目的分析肾母细胞瘤1(WT1)基因联合多参数流式细胞术检测微小残留病灶(FCM-MRD)对急性髓系白血病(AML)患儿预后的预测价值。方法回顾性分析76例AML患儿的临床资料及一般信息。患儿治疗前均采用实时荧光定量聚合酶链式反应(qRT-PCR)检测WT1基因表达,并经FCM检测MRD。所有患儿随访1年,根据预后情况的不同分为预后良好组(n=40)和预后不良组(n=36)。观察2组患儿治疗前及治疗后3、9、12个月的WT1基因及MRD变化情况;比较不同治疗方案患儿治疗前后WT1基因及MRD变化情况;分析AML患儿临床病理特征与WT1基因表达及FCM-MRD阳性率的关系。采用Spearman相关系数分析WT1基因表达、FCM-MRD阳性率与AML患儿预后的关系;绘制Kaplan-Meier生存曲线,分析WT1基因表达、FCM-MRD阳性率对AML患儿复发的影响及相关性;绘制受试者工作特征(ROC)曲线分析WT1基因、FCM-MRD单一及联合检测对AML患儿预后的预测效能;分析WT1基因、MRD与AML患儿FLT3 ITD/TKD突变的关系。结果预后良好组患儿治疗后9、12个月的WT1表达量及FCM-MRD阳性率低于预后不良组,差异有统计学意义(P<0.05);接受DAH化疗方案患儿的WT1基因表达、FCM-MRD阳性率低于接受DAE化疗方案患儿,预后良好率高于接受DAE化疗方案患儿,但差异无统计学意义(P>0.05);WT1基因表达及FCM-MRD阳性率与AML患儿白细胞计数、FAB分型、骨髓原始细胞及细胞遗传学分组具有相关性(P<0.05)。Spearman相关系数分析显示,WT1基因表达、FCM-MRD阳性率与AML患儿预后呈显著负相关(P<0.05);Kaplan-Meier生存曲线验证显示,WT1高表达患儿总生存期(OS)、无进展生存期(PFS)均低于WT1低表达患儿,差异有统计学意义(χ^(2)=4.215、9.530,P=0.040、0.002),FCM-MRD阳性患儿OS、PFS均低于FCM-MRD阴性患儿,差异也有统计学意义(χ^(2)=5.144、6.381,P=0.023、0.012);Spearman相关系数分析显示,WT1基因表达与AML患儿OS、PFS呈显著负相关(P<0.0Objective To analyze the value of Wilms tumor 1(WT1)gene combined with multiparameter flow cytometry for minimal residual disease(FCM-MRD)in evaluating prognosis of children with acute myeloid leukemia(AML).Methods The clinical data and general information of 76 children with AML were retrospectively analyzed.Before treatment,WT1 gene expression was detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)in all the children,and MRD was detected by FCM.All the children were followed up for a year,and they were divided into good prognosis group(n=40)and poor prognosis group(n=36)according to prognosis condition.The changes of WT1 gene and MRD before treatment and 3,9 and 12 months after treatment were observed in both groups;the changes of WT1 gene and MRD before and after treatment were compared in the children with different therapeutic plans;the relationships of clinicopathological features with WT1 gene expression and positive rate of FMM-MRD were analyzed in AML children.Spearman correlation coefficient was used to analyze the relationships of WT1 gene expression and positive rate of FCM-MRD with the prognosis of AML children;the Kaplan-Meier survival curve was drawn to analyze the effects of WT1 gene expression and positive rate of FMM-MRD on the recurrence of AMLchildren and their correlations;the receiver operating characteristic(ROC)curve was drawn to analyze the efficiencies of single detection with WT1 gene and FMM-MRD and combined detection in predicting prognosis of AML children;the relationships of WT1 gen and MRD with FLT3 ITD/TKD mutation were analyzed in AML children.Results The WT1 expression levels and positive rates of FCM-MRD at 9 and 12 months after treatment in the good prognosis group were significantly lower than those in the poor prognosis group(P<0.05);the WT1 gene expression level and positive rate of FCM-MRD in children with DAH chemotherapy regimen were lower than those in children with DAE chemotherapy regimen,while the rate of good prognosis was higher than

关 键 词：肾母细胞瘤1基因 急性髓系白血病 微小残留病灶 多参数 流式细胞术 预后 

分 类 号：R733.71[医药卫生—肿瘤] R730.23[医药卫生—临床医学] R446.11