Washington University, St Louis, MO 63110, USA.
Hematology Am Soc Hematol Educ Program. 2011;2011:543-9. doi: 10.1182/asheducation-2011.1.543.
Myelodysplastic syndromes (MDS) are a heterogenous group of hematologic malignancies characterized by clonal expansion of BM myeloid cells with impaired differentiation. The identification of recurrent mutations in MDS samples has led to new insights into the pathophysiology of these disorders. Of particular interest is the recent recognition that genes involved in the regulation of histone function (EZH2, ASXL1, and UTX) and DNA methylation (DNMT3A, IDH1/IDH2, and TET2) are recurrently mutated in MDS, providing an important link between genetic and epigenetic alterations in this disease. The mechanism by which these mutated genes contribute to disease pathogenesis is an active area of research, with a current focus on which downstream target genes may be affected. Recent advances from sequencing studies suggest that multiple mutations are required for MDS initiation and progression to acute myeloid leukemia (AML). The past several years have yielded many new insights, but the complete genetic landscape of MDS is not yet known. Moreover, few (if any) of the findings are sufficiently robust to be incorporated into routine clinical practice at this time. Additional studies will be required to understand the prognostic implications of these mutations for treatment response, progression to AML, and survival.
骨髓增生异常综合征（MDS）是一组异质性的血液恶性肿瘤，其特征为骨髓髓系细胞的克隆性扩张伴有分化障碍。在 MDS 样本中鉴定出的反复突变，使人们对这些疾病的病理生理学有了新的认识。特别值得关注的是，最近发现参与组蛋白功能调节的基因（EZH2、ASXL1 和 UTX）和 DNA 甲基化（DNMT3A、IDH1/IDH2 和 TET2）在 MDS 中反复发生突变，为该疾病中遗传和表观遗传改变之间提供了重要联系。这些突变基因导致疾病发病机制的机制是一个活跃的研究领域，目前的重点是哪些下游靶基因可能受到影响。来自测序研究的最新进展表明，MDS 的起始和进展为急性髓系白血病（AML）需要多个突变。过去几年取得了许多新的认识，但 MDS 的完整遗传图谱尚不清楚。此外，目前很少（如果有的话）发现足以纳入常规临床实践。需要进一步研究来了解这些突变对治疗反应、向 AML 进展和生存的预后意义。
