CAJ | 학술논문

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.
목적 초보탐색재급성백혈병(AL)조혈간세포이식술(HSCT)후,Wilms류기인(WT1)수평대감측미소잔류병(MRD)급예측림상예후적의의.방법 채용실시정량PCR기술동태검측2001년12월지2009년9월소주대학부속제일의원혈액과63례HSCT후환자적WTl기인급관가기인ABL mRNA표체수평(공326빈골수표본).비교이식후불동전귀조환자적WT1표체수평,의거수시자공작특정(ROC)곡선학정출가예측림상복발적WT1역치,근거역치대WT1양성여음성환자예후이급간예치료효과진행분석.결과 19례복발환자WT1중위표체수평위1270(55-47 596),44례미복발환자WT1중위표체수평위132(0～2959),복발조WT1표체수평고우미복발조,차이유통계학의의(P<0.01).19례복발환자중,제1례재복발후말계속검측WT1외,10례인복발도치사망적환자WT1중위표체수평략고우기타8례환자,단차이무통계학의의(P>0.05).채용ROC곡선이wn=585위계장63례환자분위WT1양성조(>585)화음성조(<585)량조.WT1음성조환자교양성조환자구유경고적무복발생존(RFS)급총생존(OS)솔(균P<0.01).수방21례WTl양성적환자,발현재이식후3개월내、4～6개월、7～9개월화9개월후검측도WT1표체양성적환자적루적복발솔분별위:8/8,2/4,2/4,3/5(P=0.063),병차간예치료효과흠가.결론 WT1기인가이작위AL환자HSCT후독립적MRD감측지표,WT1>585위이식후환자적예후불량인소.
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.