Myeloid neoplasms originate from the clonal proliferation of hematopoietic stem cells, which is driven by the acquisition of somatic genetic mutations. Within these disorders, myelodysplastic syndromes (MDS) are specifically characterized by morphologic abnormalities (dysplasia) and impaired maturation of myeloid precursors (ineffective hematopoiesis), resulting in peripheral blood cytopenia. Several studies have advanced the field of MDS, with a few landmark papers leading to a paradigm shift, opening new avenues of research and enabling a molecular revolution. These seminal papers include the first description of the 5q- syndrome, the identification of somatic mutations of TET2 in myeloid neoplasms, the detection of common pathway mutations in the splicing machinery, and the discovery of clonal hematopoiesis. The somatic genomic landscape of MDS is now well-defined. Genes that are recurrently mutated include epigenetic regulators, as well as genes of RNA splicing machinery, transcription regulation, DNA repair control, cohesin complex, and signal transduction. Furthermore, several disorders with a germline genetic predisposition to MDS have been identified, collectively accounting for up to 15% of all MDS cases. Genomic profiling can significantly improve the diagnostic approach to MDS, allowing the identification of distinct nosologic entities such as SF3B1-mutant or TP53-mutant MDS. The Molecular International Prognostic Scoring System for MDS (IPSS-M) has already proven to be a valuable tool for individualized risk assessment and treatment decisions. In addition, the recently developed molecular taxonomy of MDS will likely facilitate the implementation of precision medicine approaches for these disorders. This will necessitate the establishment of specialized infrastructures within public health systems, involving close collaboration between healthcare institutions, academia, and the life sciences industry.

中文翻译：

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基因组测序在骨髓增生异常综合征和相关疾病管理中的应用。


髓系肿瘤起源于造血干细胞的克隆增殖，这是由体细胞基因突变的获得驱动的。在这些疾病中，骨髓增生异常综合征 （MDS） 的特异性特征是形态学异常（异型增生）和髓系前体成熟受损（无效造血），导致外周血血细胞减少症。几项研究推动了 MDS 领域的发展，一些具有里程碑意义的论文导致了范式转变，开辟了新的研究途径并促成了分子革命。这些开创性的论文包括 5q- 综合征的首次描述、髓系肿瘤中 TET2 体细胞突变的鉴定、剪接机制中常见通路突变的检测以及克隆造血的发现。MDS 的体细胞基因组景观现在已经明确定义。反复突变的基因包括表观遗传调节因子，以及 RNA 剪接机制、转录调控、DNA 修复控制、黏连蛋白复合物和信号转导的基因。此外，已经确定了几种具有 MDS 种系遗传易感性的疾病，合计占所有 MDS 病例的 15%。基因组分析可以显着改善 MDS 的诊断方法，从而可以识别不同的病学实体，例如 SF3B1 突变体或 TP53 突变体 MDS。MDS 分子国际预后评分系统 （IPSS-M） 已被证明是个体化风险评估和治疗决策的宝贵工具。此外，最近开发的 MDS 分子分类学可能会促进针对这些疾病的精准医学方法的实施。 这将需要在公共卫生系统内建立专门的基础设施，涉及医疗机构、学术界和生命科学行业之间的密切合作。