Department of Hematology, Affiliated Changzhou Second Hospital of Nanjing Medical University, Changzhou, People's Republic of China.
Department of Hematology, Wuxi Third people's hospital, Wuxi, People's Republic of China.
Hematology. 2022 Dec;27(1):994-1002. doi: 10.1080/16078454.2022.2103964.
Several studies have confirmed that mutations in the Wilms tumor 1 (WT1) gene occur in adult acute myeloid leukemia (AML). However, few data are available regarding the incidence of WT1 mutations in CEBPA AML and their impact.
We retrospectively analyzed the frequency and clinical impact of WT1 mutations in 220 newly diagnosed AML patients with CEBPA mutations(CEBPA). Chromosome karyotype analysis was performed by R or G banding method and further confirmed either by fluorescence in situ hybridization (FISH) and/or by multiple reverse transcription polymerase chain reaction (multiple RT-PCR). Mutations were detected with a panel of 112mutational genes using next-generation sequencing (NGS).
Overall, 30 WT1 mutations were detected in 29 of the 220 CEBPA AML patients (13.18%) screened. These mutations clustered overwhelmingly in exon 7 (=16). WT1 mutations were found to be significantly more frequent in AML patients with double-mutated CEBPA (CEBPA) than in AML patients with single-mutated CEBPA (17.36%. 8.08%, = 0.043). Among WT1-mutated patients, the most common co-mutation was FLT3-ITD (n = 7, 24.14%), followed by NRAS (n = 5, 17.24%), CSF3R (n = 4, 13.79%), GATA2 (n = 4, 13.79%), and KIT (n = 4, 13.79%). The most frequent functional pathway was signaling pathways inas many as 62.07% of cases. Notably,the concomitant mutations in epigenetic regulatorswere inversely correlated with WT1 mutations(= 0.003). CEBPA AML patients with WT1 mutations had inferior relapse-free survival, event-free survival and overall survival compared with patients CEBPA AML without WT1 mutations (= 0.002, 0.004, and 0.010, respectively).
Our data showed that WT1 mutations are frequently identified in CEBPA AML, especially in CEBPA AML. CEBPA AML patients with WT1 mutations show distinct spectrum of comutations. In the context of CEBPA AML, WT1 mutations predict a poor prognosis.
几项研究已经证实，WT1 基因的突变发生在成人急性髓系白血病（AML）中。然而，关于 CEBPA AML 中 WT1 突变的发生率及其影响的数据很少。
我们回顾性分析了 220 例新诊断的 CEBPA 突变（CEBPA）AML 患者中 WT1 突变的频率和临床影响。染色体核型分析采用 R 或 G 带法，进一步通过荧光原位杂交（FISH）和/或多重逆转录聚合酶链反应（多重 RT-PCR）进行确认。使用下一代测序（NGS）对 112 个突变基因进行突变检测。
在 220 例 CEBPA AML 患者中，共筛选出 29 例（13.18%）WT1 突变。这些突变主要聚集在第 7 外显子（=16）。WT1 突变在双突变 CEBPA（CEBPA）AML 患者中明显比单突变 CEBPA（CEBPA）AML 患者更为常见（17.36%、8.08%，=0.043）。在 WT1 突变患者中，最常见的共突变是 FLT3-ITD（n=7，24.14%），其次是 NRAS（n=5，17.24%）、CSF3R（n=4，13.79%）、GATA2（n=4，13.79%）和 KIT（n=4，13.79%）。信号通路是最常见的功能途径，占比高达 62.07%。值得注意的是，表观遗传调节剂的共突变与 WT1 突变呈负相关（=0.003）。与无 WT1 突变的 CEBPA AML 患者相比，CEBPA AML 患者伴 WT1 突变的患者无复发生存率、无事件生存率和总生存率均较差（=0.002、0.004 和 0.010）。
我们的数据表明，WT1 突变在 CEBPA AML 中经常发生，尤其是在 CEBPA AML 中。伴有 WT1 突变的 CEBPA AML 患者具有独特的共突变谱。在 CEBPA AML 中，WT1 突变预示着预后不良。
