Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Myeloid Malignancies Program, National Institutes of Health, Bethesda, MD.
Blood Adv. 2023 Aug 22;7(16):4381-4394. doi: 10.1182/bloodadvances.2023010098.
Approximately 90% of patients with myelodysplastic syndromes (MDSs) have somatic mutations that are known or suspected to be oncogenic in the malignant cells. The genetic risk stratification of MDSs has evolved substantially with the introduction of the clinical molecular international prognostic scoring system, which establishes next-generation sequencing at diagnosis as a standard of care. Furthermore, the International Consensus Classification of myeloid neoplasms and acute leukemias has refined the MDS diagnostic criteria with the introduction of a new MDS/acute myeloid leukemia category. Monitoring measurable residual disease (MRD) has historically been used to define remission status, improve relapse prediction, and determine the efficacy of antileukemic drugs in patients with acute and chronic leukemias. However, in contrast to leukemias, assessment of MRD, including tracking of patient-specific mutations, has not yet been formally defined as a biomarker for MDS. This article summarizes current evidence and challenges and provides a conceptual framework for incorporating MRD into the treatment of MDS and future clinical trials.
大约 90%的骨髓增生异常综合征 (MDS) 患者存在已知或疑似恶性细胞中致癌的体细胞突变。随着临床分子国际预后评分系统的引入,MDS 的遗传风险分层发生了重大变化,该系统将诊断时的下一代测序确立为标准护理。此外,髓系肿瘤和急性白血病的国际共识分类通过引入新的 MDS/急性髓系白血病类别,对 MDS 诊断标准进行了细化。监测可测量残留疾病 (MRD) 历史上用于定义缓解状态、提高复发预测,并确定急性和慢性白血病患者中抗白血病药物的疗效。然而,与白血病不同,MRD 的评估,包括患者特异性突变的跟踪,尚未被正式定义为 MDS 的生物标志物。本文总结了当前的证据和挑战,并为将 MRD 纳入 MDS 的治疗和未来临床试验提供了概念框架。