U2AF1 表达是儿童 T 细胞急性淋巴细胞白血病的一个新的独立预后指标。
U2AF1 expression is a novel and independent prognostic indicator of childhood T-lineage acute lymphoblastic leukemia.
机构信息
Department of Hematology-Oncology, Pediatric Hematology-Oncology Center, Zhejiang Provincial Pediatric Leukemia Diagnostic and Therapeutic Research Center, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Children's Hospital of Shanxi Province, Taiyuan, China.
出版信息
Int J Lab Hematol. 2021 Aug;43(4):675-682. doi: 10.1111/ijlh.13433. Epub 2020 Dec 13.
INTRODUCTION
U2AF1 gene is associated with various types of hematological malignancies in adults. However, the expression level of U2AF1 gene and its prognostic significance are unclear in pediatric ALL patients. The study aimed to study the mRNA level of U2AF1 in pediatric ALL patients and its clinical relevance with long-term survival.
METHODS
We quantitatively determined U2AF1 gene expression at diagnosis in 132 children with ALL by real-time PCR. According to the patients' median U2AF1 value, the patients' samples were classified into low U2AF1 and high U2AF1 expression groups. Twenty-two bone marrow samples from 22 patients with ITP were recruited as control. The correlation between the expression level of U2AF1 and clinical treatment outcome was analyzed.
RESULTS
Pediatric patients with ALL showed higher U2AF1 mRNA levels than controls (P = .034). The relapse rates of patients in low U2AF1 levels group were obviously higher than those of U2AF1 high expression group (28.8% vs 12.1%, P = .030). Patients of low U2AF1 expression presented worse 5-year EFS than those of high U2AF1 expression (60% vs 81%, P = .035). For T-ALL, patients with low U2AF1 mRNA level showed lower BM blast percentages (P = .031), worse EFS (37.8% vs 92.3%, P = .003), and CIR (62.2% vs 7.7%, P = .003) than those in high U2AF1 expression group. Multivariate analysis confirmed low U2AF1 mRNA level could be used as an independent risk indicator of poor EFS and CIR of children with T-ALL.
CONCLUSION
Low U2AF1 mRNA level is related to inferior prognosis and can be served as a prognostic indicator for risk stratification in children with T-ALL.
简介
U2AF1 基因与成人各种类型的血液系统恶性肿瘤有关。然而，U2AF1 基因的表达水平及其在儿科 ALL 患者中的预后意义尚不清楚。本研究旨在研究儿科 ALL 患者 U2AF1 的 mRNA 水平及其与长期生存的临床相关性。
方法
我们通过实时 PCR 定量测定了 132 例 ALL 患儿诊断时 U2AF1 基因的表达。根据患者的中位数 U2AF1 值，将患者样本分为低 U2AF1 和高 U2AF1 表达组。招募了 22 例 ITP 患者的 22 例骨髓样本作为对照。分析了 U2AF1 表达水平与临床治疗结果的相关性。
结果
ALL 患儿 U2AF1 mRNA 水平高于对照组（P=0.034）。低 U2AF1 水平组患者的复发率明显高于 U2AF1 高表达组（28.8%比 12.1%，P=0.030）。低 U2AF1 表达组患者的 5 年 EFS 明显低于 U2AF1 高表达组（60%比 81%，P=0.035）。对于 T-ALL，低 U2AF1 mRNA 水平的患者骨髓原始细胞百分比较低（P=0.031），EFS 较差（37.8%比 92.3%，P=0.003），CIR 较高（62.2%比 7.7%，P=0.003）。多变量分析证实，低 U2AF1 mRNA 水平可作为 T-ALL 患儿 EFS 和 CIR 不良的独立危险因素。
结论
低 U2AF1 mRNA 水平与预后不良相关，可作为 T-ALL 患儿危险分层的预后指标。
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