急性白血病造血干细胞移植后WTl基因检测与临床预后的相关性  

Correlation between clinical outcome and WT1 detection after hematopoietic stem cell transplantation in acute leukemia

作　　者：赵丙瑞[1] 唐晓文[1] 岑建农[1] 金松[1] 施晓兰[1] 魏孝艾[1] 常伟荣[1] 孙爱宁[1] 吴德沛[1] 

机构地区：[1]苏州大学附属第一医院血液科江苏省血液研究所卫生部血栓与止血重点实验室,215006

出　　处：《中华医学杂志》2011年第20期1375-1378,共4页National Medical Journal of China

基　　金：江苏省“科教兴卫”工程医学重点人才资助项目（RC2007072）;江苏省人事厅“六大人才高峰”资助项目（07-B-019）;苏州市国际科技合作项目（SWH0815）;苏州市科技计划应用基础项目（YJS0912）

摘　　要：目的 初步探索在急性白血病（AL）造血干细胞移植术（HSCT）后,Wilms瘤基因（WT1）水平对监测微小残留病（MRD）及预测临床预后的意义.方法 采用实时定量PCR技术动态检测2001年12月至2009年9月苏州大学附属第一医院血液科63例HSCT后患者的WTl基因及管家基因ABL mRNA表达水平（共326份骨髓标本）.比较移植后不同转归组患者的WT1表达水平,依据受试者工作特征（ROC）曲线确定出可预测临床复发的WT1阈值,根据阈值对WT1阳性与阴性患者预后以及干预治疗效果进行分析.结果 19例复发患者WT1中位表达水平为1270（55-47 596）,44例未复发患者WT1中位表达水平为132（0～2959）,复发组WT1表达水平高于未复发组,差异有统计学意义（P〈0.01）.19例复发患者中,除1例在复发后末继续检测WT1外,10例因复发导致死亡的患者WT1中位表达水平略高于其他8例患者,但差异无统计学意义（P〉0.05）.采用ROC曲线以wn=585为界将63例患者分为WT1阳性组（〉585）和阴性组（〈585）两组.WT1阴性组患者较阳性组患者具有更高的无复发生存（RFS）及总生存（OS）率（均P〈0.01）.随访21例WTl阳性的患者,发现在移植后3个月内、4～6个月、7～9个月和9个月后检测到WT1表达阳性的患者的累积复发率分别为：8/8,2/4,2/4,3/5（P=0.063）,并且干预治疗效果欠佳.结论 WT1基因可以作为AL患者HSCT后独立的MRD监测指标,WT1〉585为移植后患者的预后不良因素.Objective To evaluate preliminarily the significance of detecting the Wilms＇tumor （WT1）gene level on monitoring minimal residual disease（MRD）and predicting the clinical outcome in patients of acute leukemia following hematopoietic stem cell transplantation（HSCT）.nethods The Mrna expression levels of WT1 and house-keeping gene ABL were dynamically measured with Real-time quantitative reverse transcription polymerase chain reaction（RQ-RT-PCR）on 326 bone marrow samples from 63 post-HSCT patients in our hospital from December 2001 to September 2009.After comparing the WT1 levels of patients with difierent post-transplantation outcomes,the investigators used the receiver operating characteristic（ROC）curve to determine the WT1 threshold so as to predict their clinical relapses.Then different prognoses of WT1 positive and negative patients were analyzed.Results The levels of WT1expression showed significant difierence between the 19 relapsing and 44 non-relapsing patients with the median expression levels of 1270（55-47 596）and 132（0-2959）respectively（P〈0.01）.In 19relapsing patients,except for 1 patient discontinuing the detection of WT1,10 mortality cases due to recurrence had higher levels of WT1 expression than other 8 patients（P〉0.05）.According to the ROC curve,the cut-off value of WT1 at 585 could separate 63 patients into the WT1-positive group（〉585）and were followed up for 3,4-6,7-9 and 9 months respectively.The cumulative post-HSCT recurrence rates in those WT1-positive cases were 8/8,2/4,2/4 and 3/5（P=0.063）respectively.And the intervention was ineffective.Conclusions WT1 gene may be an independent factor of monitoring MRD.And WT1〉585 is a poor post-HSCT prognostic factor for the Patients of acute leukemia.

关 键 词：白血病 造血干细胞移植 WT1基因 微小残留病 预后 

分 类 号：R733.71[医药卫生—肿瘤]