Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Ann Hematol. 2024 Sep;103(9):3639-3648. doi: 10.1007/s00277-024-05681-4. Epub 2024 Mar 7.
Epigenetic modifier (EM) genes play important roles in the occurrence and progression of acute lymphoblastic leukemia (ALL). However, the prognostic significance of EM mutations in ALL has not yet been thoroughly investigated. This retrospective study included 205 adult patients with ALL engaged in a pediatric-type regimen. Based on targeted next-generation sequencing, they were divided into EM mutation group (EM-mut, n = 75) and EM wild-type group (EM-wt, n = 130). The EM-mut group showed a higher positive rate of minimal residual disease (MRD) on treatment day24 and before consolidation therapy (P = 0.026, 0.020). Multivariate Cox regression analysis showed that EM-mut was an independent adverse factor for overall survival (OS) and event-free survival (EFS) (HR = 2.123, 1.742; P = 0.009, 0.007). Survival analysis revealed that the OS and EFS rates were significantly lower in the EM-mut group than in the EM-wt group (3-year OS rate, 45.8% vs. 65.0%, P = 0.0041; 3-year EFS rate, 36.7% vs. 53.2%, P = 0.011). In conclusion, EM was frequently mutated in adult ALL and was characterized by poor response to induction therapy and inferior clinical outcomes.
表观遗传修饰（EM）基因在急性淋巴细胞白血病（ALL）的发生和进展中发挥重要作用。然而，EM 突变在 ALL 中的预后意义尚未得到充分研究。本回顾性研究纳入了 205 例接受儿童型方案治疗的成人 ALL 患者。基于靶向下一代测序，他们被分为 EM 突变组（EM-mut，n=75）和 EM 野生型组（EM-wt，n=130）。EM-mut 组在治疗第 24 天和巩固治疗前的微小残留病（MRD）阳性率更高（P=0.026，0.020）。多变量 Cox 回归分析显示，EM-mut 是总生存（OS）和无事件生存（EFS）的独立不良因素（HR=2.123，1.742；P=0.009，0.007）。生存分析显示，EM-mut 组的 OS 和 EFS 率明显低于 EM-wt 组（3 年 OS 率，45.8% vs. 65.0%，P=0.0041；3 年 EFS 率，36.7% vs. 53.2%，P=0.011）。总之，成人 ALL 中 EM 经常发生突变，表现为诱导治疗反应不良和临床结局较差。
