Cook Michael R, Karp Judith E, Lai Catherine
Division of Hematology and Oncology Lombardi Comprehensive Cancer Center Georgetown University Hospital Washington District of Columbia USA.
Divison of Hematology and Oncology The Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Hospital Baltimore Maryland USA.
EJHaem. 2021 Nov 1;3(1):301-313. doi: 10.1002/jha2.317. eCollection 2022 Feb.
The natural history of patients with myelodysplastic syndrome (MDS) is dependent upon the presence and magnitude of diverse genetic and molecular aberrations. The International Prognostic Scoring System (IPSS) and revised IPSS (IPSS-R) are the most widely used classification and prognostic systems; however, somatic mutations are not currently incorporated into these systems, despite evidence of their independent impact on prognosis. Our manuscript reviews prognostic information for TP53, EZH2, DNMT3A, ASXL1, RUNX1, SRSF2, CBL, IDH 1/2, TET2, BCOR, ETV6, GATA2, U2AF1, ZRSR2, RAS, STAG2, and SF3B1. Mutations in TP53, EZH2, ASXL1, DNMT3A, RUNX1, SRSF2, and CBL have extensive evidence for their negative impact on survival, whereas SF3B1 is the lone mutation carrying a favorable prognosis. We use the existing literature to propose the incorporation of somatic mutations into the IPSS-R. More data are needed to define the broad spectrum of other genetic lesions, as well as the impact of variant allele frequencies, class of mutation, and impact of multiple interactive genomic lesions. We postulate that the incorporation of these data into MDS prognostication systems will not only enhance our therapeutic decision making but lead to targeted treatment in an attempt to improve outcomes in this formidable disease.
骨髓增生异常综合征（MDS）患者的自然病史取决于多种基因和分子异常的存在及程度。国际预后评分系统（IPSS）和修订后的IPSS（IPSS-R）是应用最广泛的分类和预后系统；然而，尽管有证据表明体细胞突变对预后有独立影响，但目前这些系统并未纳入体细胞突变情况。我们的手稿回顾了TP53、EZH2、DNMT3A、ASXL1、RUNX1、SRSF2、CBL、IDH 1/2、TET2、BCOR、ETV6、GATA2、U2AF1、ZRSR¬2、RAS、STAG2和SF3B1的预后信息。TP53、EZH2、ASXL1、DNMT3A、RUNX1、SRSF2和CBL中的突变对生存有负面影响已有大量证据，而SF3B1是唯一具有良好预后的突变。我们利用现有文献提议将体细胞突变纳入IPSS-R。还需要更多数据来明确其他基因损伤的广泛范围，以及变异等位基因频率、突变类型和多个相互作用基因组损伤的影响。我们推测，将这些数据纳入MDS预后系统不仅会改善我们的治疗决策，还会促成靶向治疗，以期改善这种难治性疾病的治疗结果。
