Erasmus University Medical Center, Department of Hematology, Dr Molewaterplein 50, 3015 GE Rotterdam, the Netherlands.
J Clin Oncol. 2010 Apr 20;28(12):2101-7. doi: 10.1200/JCO.2009.26.0646. Epub 2010 Mar 22.
PURPOSE The purpose of this study was to investigate frequency and prognostic significance of high EVI1 expression in acute myeloid leukemia (AML). PATIENTS AND METHODS A diagnostic assay detecting multiple EVI1 splice variants was developed to determine the relative EVI1 expression by single real-time quantitative polymerase chain reaction in 1,382 newly diagnosed adult patients with AML younger than 60 years. Patients were treated on four Dutch-Belgian HOVON (n = 458) and two German-Austrian AML Study Group protocols (n = 924). Results The EVI1 assay was tested in the HOVON cohort and validated in the AMLSG cohort. High EVI1 levels (EVI1(+)) were found with similar frequencies in both cohorts combined, with a 10.7% incidence (148 of 1,382). EVI1(+) independently predicted low complete remission (CR) rate (odds ratio, 0.54; P = .002), adverse relapse-free survival (RFS; hazard ratio [HR], 1.32; P = .05), and event-free survival (EFS; HR, 1.46; P < .001). This adverse prognostic impact was more pronounced in the intermediate cytogenetic risk group (EFS; HR, 1.64; P < .001; and RFS; HR, 1.55; P = .02), and was also apparent in cytogenetically normal AML (EFS; HR, 1.67; P = .008). Besides inv(3)/t(3;3), EVI1(+) was significantly associated with chromosome abnormalities monosomy 7 and t(11q23), conferring prognostic impact within these two cytogenetic subsets. EVI1(+) was virtually absent in favorable-risk AML and AML with NPM1 mutations. Patients with EVI1(+) AML (n = 28) who received allogeneic stem cell transplantation in first CR had significantly better 5-year RFS (33% +/- 10% v 0%). CONCLUSION EVI1 expression in AML is unequally distributed in cytogenetic subtypes. It predicts poor outcome, particularly among intermediate cytogenetic risk AML. Patients with EVI1(+) AML may benefit from allogeneic transplantation in first CR. Pretreatment EVI1 screening should be included in risk stratification.
目的 本研究旨在探讨急性髓系白血病（AML）中 EVI1 高表达的频率及其预后意义。
患者与方法 我们开发了一种诊断性检测方法，用于通过单重实时定量聚合酶链反应检测多种 EVI1 剪接变异体，以确定 1382 例年龄小于 60 岁的新诊断成人 AML 患者的相对 EVI1 表达。患者接受了四项荷兰-比利时 HOVON（n = 458）和两项德国-奥地利 AML 研究组方案（n = 924）的治疗。
结果 EVI1 检测方法在 HOVON 队列中进行了检测，并在 AMLSG 队列中进行了验证。在两个队列的组合中，EVI1(+) 的发生率相似，为 10.7%（148/1382）。EVI1(+)独立预测低完全缓解（CR）率（比值比，0.54；P =.002）、不良无复发生存（RFS；风险比 [HR]，1.32；P =.05）和无事件生存（EFS；HR，1.46；P <.001）。这种不良预后影响在中间细胞遗传学风险组中更为明显（EFS；HR，1.64；P <.001；RFS；HR，1.55；P =.02），在细胞遗传学正常的 AML 中也同样明显（EFS；HR，1.67；P =.008）。除 inv(3)/t(3;3) 外，EVI1(+)还与单体 7 和 t(11q23)染色体异常显著相关，在这两个细胞遗传学亚组中具有预后影响。EVI1(+)在有利风险 AML 和 NPM1 突变的 AML 中几乎不存在。在首次 CR 接受异基因干细胞移植的 EVI1(+) AML 患者（n = 28）中，5 年 RFS 显著提高（33% +/- 10% v 0%）。
结论 AML 中的 EVI1 表达在细胞遗传学亚型中分布不均。它预测不良预后，尤其是在中间细胞遗传学风险 AML 中。EVI1(+) AML 患者可能从首次 CR 中的异基因移植中获益。治疗前 EVI1 筛查应纳入风险分层。
