Biochemistry Subdivision, Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt.
Hematology Unit, Clinical Pathology Department, Mansoura University Oncology Center, Mansoura University, Mansoura, Egypt.
Asian Pac J Cancer Prev. 2023 Apr 1;24(4):1257-1264. doi: 10.31557/APJCP.2023.24.4.1257.
The objective of the present study was to improve the risk stratification of T-cell Acute Lymphoblastic Leukemia (T-ALL) patients. It aimed to identify the frequency and clinical impact of DNM2 gene mutations among adult T-ALL cases.
The current study included 25 T-ALL patients before starting their treatment. Mutational analysis of DNM2 gene (exons 18 and 22) was performed for all patients using Macrogen 3730 apparatus.
We identified DNM2 gene mutations in 19 out of 25 (76%) patients. The detected mutations were either missense or deletion. Only active mutations (deletion) were associated with poor induction remission response and high frequency of relapse. Two novel mutations were addressed among the studied cohort of patients. They included c.1866G>C (p.V596L) and c.1872delA in exon 18. A high frequency of silent mutations was also found in T-ALL patients, but with no impact on clinical features.
The DNM2 mutations were prevalent among adult T-ALL patients and might have a role in the pathogenesis of the disease. Active DNM2 mutations were associated with poor clinical outcome. Moreover, high frequency of DNM2 mutations indicated that these mutations could be utilized in detection of minimal residual disease in T-ALL patients.
本研究的目的是改善 T 细胞急性淋巴细胞白血病（T-ALL）患者的风险分层。旨在确定 DNM2 基因突变在成人 T-ALL 病例中的频率和临床影响。
本研究纳入了 25 名开始治疗前的 T-ALL 患者。使用 Macrogen 3730 仪器对所有患者的 DNM2 基因（外显子 18 和 22）进行突变分析。
我们在 25 名患者中的 19 名（76%）中发现了 DNM2 基因突变。检测到的突变要么是错义要么是缺失。只有活性突变（缺失）与诱导缓解反应不良和高复发率相关。在研究的患者队列中发现了两种新的突变。它们包括外显子 18 中的 c.1866G>C（p.V596L）和 c.1872delA。在 T-ALL 患者中还发现了高频率的沉默突变，但对临床特征没有影响。
DNM2 突变在成人 T-ALL 患者中较为常见，可能在疾病发病机制中起作用。活性 DNM2 突变与不良的临床结局相关。此外，DNM2 突变的高频率表明这些突变可用于检测 T-ALL 患者的微小残留病。
