Abstract

Abnormally high ecotropic viral integration site 1 (EVI1) expression has been recognized as a poor prognostic factor in acute myeloid leukemia patients. However, its prognostic impact in B cell precursor acute lymphoblastic leukemia (BCP-ALL) remains unknown. A total of 176 pediatric Ph-negative BCP-ALL patients who received at least 1 course of chemotherapy and received chemotherapy only during follow-up were retrospectively tested for EVI1 transcript levels by real-time quantitative PCR at diagnosis, and survival analysis was performed. Clinical and EVI1 expression data of 129 pediatric BCP-ALL patients were downloaded from therapeutically applicable research to generate effective treatments (TARGET) database for validation. In our cohort, the median EVI1 transcript level was 0.33% (range, 0.0068–136.2%), and 0.10% was determined to be the optimal cutoff value for patient grouping by receiver operating characteristic curve analysis. Low EVI1 expression (<0.10%) was significantly related to lower 5-year relapse-free survival (RFS) and overall survival (OS) rates (P = 0.017 and 0.018, respectively). Multivariate analysis showed that EVI1 expression <0.10% was an independent adverse prognostic factor for RFS and OS. TARGET data showed that low EVI1 expression tended to be related to a lower 5-year OS rate (P = 0.066). In conclusion, low EVI1 expression at diagnosis could predict poor outcomes in pediatric Ph-negative BCP-ALL patients receiving chemotherapy.

Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1939818 .

摘要

异常高的亲嗜性病毒整合位点 1 (EVI1) 表达已被认为是急性髓细胞白血病患者的不良预后因素。然而，它对 B 细胞前体急性淋巴细胞白血病 (BCP-ALL) 的预后影响仍然未知。对共接受至少1个疗程化疗且仅在随访期间接受化疗的176例儿童Ph阴性BCP-ALL患者在诊断时通过实时定量PCR进行回顾性检测EVI1转录水平，并进行生存分析。从治疗适用的研究中下载了 129 名儿科 BCP-ALL 患者的临床和 EVI1 表达数据，以生成有效治疗 (TARGET) 数据库进行验证。在我们的队列中，EVI1 转录水平中位数为 0.33%（范围 0.0068-136.2%）和 0。通过受试者工作特征曲线分析确定 10% 是患者分组的最佳截止值。低 EVI1 表达 (<0.10%) 与较低的 5 年无复发生存 (RFS) 和总生存 (OS) 率显着相关。P  = 0.017 和 0.018，分别）。多因素分析显示EVI1表达<0.10%是RFS和OS的独立不良预后因素。TARGET 数据显示，低 EVI1 表达倾向于与较低的 5 年 OS 率相关（P  = 0.066）。总之，诊断时的低 EVI1 表达可以预测接受化疗的儿童 Ph 阴性 BCP-ALL 患者的不良预后。

本文的补充数据可在 https://doi.org/10.1080/08880018.2021.1939818 在线获取。