骨髓增生异常综合症（MDS）包括一组血液恶性肿瘤，其特征为造血不良、细胞遗传学异常，并经常高风险转化为急性髓系白血病（AML）。到目前为止，仅有极少数研究评估了表观遗传学组分对这些疾病病理生理学的贡献，但没有一项研究在基因组范围内评估这一点。在这里，我们实施了一种通用的高通量表观基因组学方法，使用LpnPI消化片段的甲基化DNA测序（MeD-seq）来识别与MDS亚型相关的潜在表观基因组靶点。我们的结果突出显示，PCDHG和ZNF基因家族具有潜在的表观基因组靶点，在不同MDS亚型之间的多种比较中已被证明有不同的甲基化。具体而言，ZNF124、ZNF497和PCDHG家族内的CpG岛、转录起始位点和转录后起始位点的甲基化差异大于3.5倍。总的来说，这些发现突出了MDS综合症病理发病的表观基因组学组分和低甲基化剂药物治疗反应的药理表观遗传学基础的重要方面，而这种通用的高通量全表观基因组测序方法可以轻松地应用于具有较强表观遗传组分的其他遗传疾病。©2023作者。

Myelodysplastic syndromes (MDS) consist of a group of hematological malignancies characterized by ineffective hematopoiesis, cytogenetic abnormalities, and often a high risk of transformation to acute myeloid leukemia (AML). So far, there have been only a very limited number of studies assessing the epigenetics component contributing to the pathophysiology of these disorders, but not a single study assessing this at a genome-wide level. Here, we implemented a generic high throughput epigenomics approach, using methylated DNA sequencing (MeD-seq) of LpnPI digested fragments to identify potential epigenomic targets associated with MDS subtypes. Our results highlighted that PCDHG and ZNF gene families harbor potential epigenomic targets, which have been shown to be differentially methylated in a variety of comparisons between different MDS subtypes. Specifically, CpG islands, transcription start sites and post-transcriptional start sites within ZNF124, ZNF497 and PCDHG family are differentially methylated with fold change above 3,5. Overall, these findings highlight important aspects of the epigenomic component of MDS syndromes pathogenesis and the pharmacoepigenomic basis to the hypomethylating agents drug treatment response, while this generic high throughput whole epigenome sequencing approach could be readily implemented to other genetic diseases with a strong epigenetic component.© 2023. The Author(s).