Xu Jing, Zhang Yaofang, Hu Jinjun, Ren Yan, Wang Hongwei
The Second Clinical Medical College, Shanxi Medical University, Taiyuan, People's Republic of China.
Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China.
Hematology. 2020 Dec;25(1):79-84. doi: 10.1080/16078454.2020.1720102.
To explore the clinical features and prognosis of normal karyotype acute myeloid leukemia (NK-AML) pediatric patients with WT1 mutations. The clinical data and prognostic information of 220 NK-AML pediatric patients were selected from target-AML project of The Cancer Genome Atlas (TCGA) database. Survival analyses were performed for NK-AML pediatric patients with different combinations of mutations. We found that 28(12.7%) NK-AML patients harbored WT1 mutations. The positive rate of FLT3-ITD in the WT1-mutated group was higher than that in the WT1 wild-type group (= 0.002). In contrast, WT1 mutation and NPM1 mutation were mutually exclusive (= 0.013). Furthermore, the WT1-mutated group suffered lower rates of complete remission (CR) (< 0.001 and < 0.001, respectively) but higher rates of minimal residual disease (MRD) (= 0.003 and = 0.021, respectively) after both one and two courses of induction chemotherapy. Patients with WT1 mutations had significantly worse overall survival (OS) and event-free survival (EFS) in both univariate (< 0.001 and = 0.007, respectively) and multivariate survival analyses (< 0.001 and < 0.001, respectively). The stratification analysis showed that for FLT3-ITD positive patients, WT1 mutations predicted shorter OS (= 0.003) and EFS (< 0.001). WT1 mutations conferred an independent poor prognosis for NK-AML pediatric patients.
探讨伴有WT1突变的核型正常的儿童急性髓系白血病（NK-AML）患者的临床特征及预后。从癌症基因组图谱（TCGA）数据库的target-AML项目中选取220例NK-AML儿童患者的临床资料及预后信息。对具有不同突变组合的NK-AML儿童患者进行生存分析。我们发现28例（12.7%）NK-AML患者存在WT1突变。WT1突变组中FLT3-ITD的阳性率高于WT1野生型组（P = 0.002）。相反，WT1突变与NPM1突变相互排斥（P = 0.013）。此外，WT1突变组在诱导化疗1个疗程和2个疗程后完全缓解（CR）率较低（分别为P < 0.001和P < 0.001），但微小残留病（MRD）率较高（分别为P = 0.003和P = 0.021）。WT1突变患者在单因素生存分析（分别为P < 0.001和P = 0.007）和多因素生存分析（分别为P < 0.001和P < 0.001）中总生存期（OS）和无事件生存期（EFS）均显著较差。分层分析显示，对于FLT3-ITD阳性患者，WT1突变预示着较短的OS（P = 0.003）和EFS（P < 0.001）。WT1突变赋予NK-AML儿童患者独立的不良预后。
