He X, Wang Q, Cen J, Qiu H, Sun A, Chen S, Wu D
Jiangsu Institute of Hematology (JIH), Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, the First Affiliated Hospital of Soochow University, Suzhou, PR China.
Collaborative Innovation Center of Hematology, Soochow University, Suzhou, PR China.
Bone Marrow Transplant. 2016 Jul;51(7):921-7. doi: 10.1038/bmt.2016.71. Epub 2016 Apr 4.
The EVI1 gene is a transcriptional regulator of hematopoietic stem cell self renewal and its overexpression is associated with adverse prognosis in de novo AML. Whether the overexpression of EVI1 also predicts poor outcome of AML patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first CR (CR1) is still unclear. Thirty-two (21.2%) out of 151 patients were categorized as high EVI1 expression (EVI1+), and 119 (78.8%) patients were categorized as low EVI1 expression (EVI1-). The frequency of EVI1+ was much higher in the adverse-risk group than the intermediate-risk group (53% vs 19%, P=0.005). EVI1+ patients were significantly likely to harbor with translocations involving the MLL gene on 11q23 (8/9). Significantly poor results were observed in the EVI1+ cohort in terms of leukemia-free survival (LFS) (in 24 months 52.6 vs 71.0%, P=0.027), overall survival (OS) (in 24 months 52.8 vs 72.4%, P=0.012), and cumulative incidence of relapse (in 24 months 39.5 vs 22.5%, P=0.013). Multivariable analysis revealed that low EVI1 expression as an independent prognostic factor favoring LFS (hazards ratio=0.47, 95% confidence interval 0.26-0.86, P=0.01) but not OS. Our results indicate high EVI1 expression might predict high risk of relapse in AML patients undergoing myeloablative allo-HSCT in CR1.
EVI1基因是造血干细胞自我更新的转录调节因子,其过表达与初发急性髓系白血病(AML)的不良预后相关。EVI1过表达是否也预示着处于首次完全缓解(CR1)期的AML患者接受清髓性异基因造血干细胞移植(allo-HSCT)后的预后不良仍不清楚。151例患者中有32例(21.2%)被归类为EVI1高表达(EVI1+),119例(78.8%)患者被归类为EVI1低表达(EVI1-)。EVI1+在不良风险组中的频率远高于中危组(53%对19%,P=0.005)。EVI1+患者显著更易发生涉及11q23上MLL基因的易位(8/9)。在无白血病生存期(LFS)(24个月时为52.6%对71.0%,P=0.027)、总生存期(OS)(24个月时为52.8%对72.4%,P=0.012)和复发累积发生率(24个月时为39.5%对22.5%,P=0.013)方面,EVI1+队列的结果显著较差。多变量分析显示,低EVI1表达是有利于LFS的独立预后因素(风险比=0.47,95%置信区间0.26-0.86,P=0.01),但对OS无影响。我们的结果表明,EVI1高表达可能预示着处于CR1期接受清髓性allo-HSCT的AML患者有高复发风险。