文章：

下一代测序技术在急性髓系白血病及骨髓增生异常肿瘤可测量残留病灶监测中的整合应用

Integration of Next-Generation Sequencing in Measurable Residual Disease Monitoring in Acute Myeloid Leukemia and Myelodysplastic Neoplasm

原文发布日期：1 September 2025

DOI: 10.3390/cancers17172874

类型: Article

开放获取: 是

英文摘要：

Background/Objectives. Recent evidence underscores the prognostic and classificatory relevance of somatic mutations in myelodysplastic neoplasms (MDSs) and acute myeloid leukemia (AML). Methods. This prospective study assessed gene mutation dynamics via next-generation sequencing (NGS) in 84 MDS/AML patients treated with intensive chemotherapy or hypomethylating agents plus venetoclax. Results. At diagnosis, 95% had somatic mutations detected by NGS, while only 29% had a measurable residual disease (MRD) marker with qPCRs. NGS at complete remission (CR) was performed in 56/71 patients who achieved CR; 59% had persisting mutations, mostly in DNMT3A, TET2, and ASXL1 (DTA mutations). Mutations’ persistence in CR was linked to a shorter relapse-free survival (RFS; median 8 months vs. not reached, HR 4.41, 95% CI 1.69–11.49;p= 0.002) and overall survival (OS; 2-year OS: 51.5% vs. 88%, HR 4.02, 95% CI 1.39–11.65;p= 0.001). Combining NGS and multiparameter flow cytometry (MFC) for MRD detection, we divided patients into three groups with distinct RFS (NGS−/MFC−, NGS−/MFC+, or NGS+/MFC− and NGS+/MFC+), with double-negative patients displaying the best RFS (p< 0.001). In the multivariate analysis, NGS and MFC MRD+ were independent predictors of RFS. Conclusions. This real-world study confirms the added prognostic role of NGS in MRD detection on RFS, particularly when combined with MFC. This approach may improve risk stratification and guide treatment decisions.

摘要翻译： 

背景/目的：近期研究证实，体细胞突变在骨髓增生异常肿瘤（MDS）和急性髓系白血病（AML）的预后评估和疾病分型中具有重要意义。方法：本前瞻性研究通过二代测序技术，对84例接受强化化疗或去甲基化药物联合维奈克拉治疗的MDS/AML患者进行基因突变动态监测。结果：初诊时，95%的患者通过NGS检测到体细胞突变，而仅29%的患者可通过定量PCR检测到可测量的残留病灶标志物。在71例达到完全缓解的患者中，对56例进行了CR期NGS检测，其中59%存在持续突变，主要集中在DNMT3A、TET2和ASXL1基因（DTA突变）。CR期突变持续存在与较短的无复发生存期相关（中位RFS：8个月 vs 未达到，HR=4.41，95%CI 1.69-11.49，p=0.002），也与较短的总生存期相关（2年OS：51.5% vs 88%，HR=4.02，95%CI 1.39-11.65，p=0.001）。通过联合NGS与多参数流式细胞术进行MRD检测，可将患者分为具有显著RFS差异的三组（NGS−/MFC−、NGS−/MFC+、NGS+/MFC−及NGS+/MFC+），其中双阴性患者RFS最佳（p<0.001）。多变量分析显示NGS与MFC MRD阳性均为RFS的独立预测因子。结论：这项真实世界研究证实，NGS在MRD检测中具有增强RFS预后评估的价值，尤其与MFC联合应用时效果显著。该策略有望优化风险分层并指导治疗决策。

原文链接：

Integration of Next-Generation Sequencing in Measurable Residual Disease Monitoring in Acute Myeloid Leukemia and Myelodysplastic Neoplasm