急性T淋巴细胞白血病异基因造血干细胞移植后WT1基因表达及其与预后关系  

The relationship between WT1 expression level and prognosis in patients of acute T lymphoblastic leukemia following allogeneic hematopoietic stem cell transplantation

作　　者：张博[1] 赵晓甦[1] 秦亚溱[1] 王昱[1] 闫晨华[1] 许兰平[1] 张晓辉[1] 刘开彦[1] 黄晓军[1] 

机构地区：[1]北京大学人民医院、北京大学血液病研究所,造血干细胞移植治疗血液病北京市重点实验室,100044

出　　处：《中华血液学杂志》2015年第8期642-646,共5页Chinese Journal of Hematology

基　　金：首都临床特色应用研究项目（Z121107001012085）;北京市自然科学基金面上项目（7132181）;国家自然科学基金青年基金（81300440）

摘　　要：目的探讨监测WT1基因在急性T淋巴细胞白血病（T-ALL）患者异基因造血干细胞移植（allo—HSCT）后预后的意义。方法回顾性分析2009年1月至2012年3月在我单位行allo-HSCT，且移植后连续监测WT1基因表达水平的68例T-ALL患者。留取初治，移植前，＋30、＋60、＋90、＋180、＋270、＋360d骨髓标本，用实时定量聚合酶链反应（RQ-PCR）方法监测WT1基因表达水平，同时经流式细胞术（FCM）监测微小残留病（MRD）。结果①移植后WT1基因低水平表达与较低复发风险相关；②＋60、＋90d WT1基因升高与较高累计复发率相关（P〈0．001、P=0．003），与较低的无病生存率（P=0．004、P=0．006）和总生存率相关（P=0．004、P=0．007）；③移植后微小残留病（MRD）阳性是T-ALL移植后复发的独立危险因素；④联合WT1基因和FCM可用于移植后复发的监测。结论＋60、＋90d WT1基因升高与T-ALL预后显著相关，应尽早予以干预，减少复发甚至死亡风险。T-ALL移植后WT1基因表达低于0．6％，复发风险较低；WT1基因表达超过0．6％需密切随访，并结合FCM监测，达到MRD阳性标准需临床干预，降低复发率。Objective To probe monitoring Wilms tumor- 1 （WT1） gene expression level in acute T lymphoblastic leukemia （T-ALL） following allogeneic hematopoietic stem cell transplantation （allo- HSCT） with prognostic significance. Methods This retrospective study analyzed 68 T-ALL cases from January 2009 to March 2012, that monitoring WT1 gene expression level after allo-HSCT. WT1 expression level was measured with real-time quantitative reverse transcription polymerase chain reaction （RQ-PCR） method at ＋ 30, ＋ 60, ＋ 90, ＋ 180, ＋ 270, ＋ 360 days after allo-HSCT, simultaneously monitoring residual leukemia using flow cytometry （FCM）. Results Low WTI gene expression level associated with a low risk of recurrence after allo-HSCT in T-ALL. Increased WTt gene expression levels at ＋60 and ＋ 90 days after allo-HSCT associated with higher cumulative incidences of relapse （P〈0.001, P=0.003）, and low disease-free survival rates （P=0.004, P=0.006）, and low overall survival rates （P=0.004, P=0.007）. The presence of MRD after allo-HSCT was an independent prognostic factor for relapse in T-ALL. Combining WT1 gene and FCM could be used to monitor recurrence after allo-HSCT. Conclusions Increased WT1 gene expression level at ＋60 and ＋ 90 days after allo-HSCT significantly associated with worse prognosis, that should be intervened as early as possible to reduce the risk of recurrence or death. WT1 gene expression level that was less than 0.6% associated with lower risk of recurrence. WTI gene expression more than 0.6% that needed close follow-up, combined with FCM monitoring MRD, which required intervention to reduce the relapse.

关 键 词：WT1基因 白血病 T淋巴细胞 急性 造血干细胞移植 复发 

分 类 号：R733.71[医药卫生—肿瘤]