Ye Lei, Zhang Li, Zhang Donglei, Zhao Xin, Li Yuan, Xiong Youzhen, Fang Liwei, Ge Meili, Shi Jun, Zhang Fengkui, Jing Liping
State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, National Clinical Research Center for Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 288 Nanjing Rd. Heping District, Tianjin, 300020, China.
Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China.
Ann Hematol. 2025 Aug 7. doi: 10.1007/s00277-025-06393-z.
This study aimed to assess the prevalence of somatic mutations (SMs) in severe/very severe aplastic anemia (V/SAA) and transfusion-dependent nonsevere aplastic anemia (TD-NSAA) prior to immunosuppressive therapy (IST) and their impact on treatment efficacy. Next-generation sequencing was used to analyze 114 hematopoiesis-related genes at disease onset in 312 patients. SMs were detected in 17.9% of cases, involving 25 genes, most commonly DNMT3A (14, 20.9%) and BCOR (9, 13.4%). SMs were more frequent in patients over 40 years old, predominantly with a single mutation of low variant allele frequency (< 20%). Patients with SM were older and had lower lymphocyte counts. SMs did not significantly influence hematologic responses at 3, 6, or 12 months, relapse, progression, death, survival, or failure-free survival (p > 0.05). Grouping patients by mutated genes revealed no significant differences in IST efficacy, though Group I (PIGA or BCOR/BCORL1) showed higher hematologic response rates in patients over 40 years of age. The cumulative incidence of clonal evolution was higher in Group II (DNMT3A, TET2, ASXL1, FAT1, or RUNX1), though not statistically significant. SMs in V/SAA and TD-NSAA were infrequent and did not affect IST outcomes or treatment decisions. However, the higher clonal evolution incidence in certain mutations warrants further research.
本研究旨在评估严重/极重度再生障碍性贫血（V/SAA）和输血依赖型非严重再生障碍性贫血（TD-NSAA）在免疫抑制治疗（IST）前体细胞突变（SMs）的发生率及其对治疗效果的影响。采用二代测序技术对312例患者疾病初发时的114个造血相关基因进行分析。17.9%的病例检测到SMs，涉及25个基因，最常见的是DNMT3A（14例，20.9%）和BCOR（9例，13.4%）。40岁以上患者的SMs更为常见，主要为单个低变异等位基因频率（<20%）的突变。有SMs的患者年龄较大，淋巴细胞计数较低。SMs对3个月、6个月或12个月时的血液学反应、复发、进展、死亡、生存或无失败生存均无显著影响（p>0.05）。按突变基因对患者进行分组显示，IST疗效无显著差异，尽管第一组（PIGA或BCOR/BCORL1）在40岁以上患者中显示出较高的血液学反应率。第二组（DNMT3A、TET2、ASXL1、FAT1或RUNX1）的克隆进化累积发生率较高，尽管无统计学意义。V/SAA和TD-NSAA中的SMs不常见，不影响IST结果或治疗决策。然而某些突变中较高的克隆进化发生率值得进一步研究。
