Myelodysplastic syndromes (MDS) are a genetically complex and phenotypically diverse set of clonal hematologic neoplasms that occur with increasing frequency with age. MDS has long been associated with systemic inflammatory conditions and disordered inflammatory signaling is implicated in MDS pathogenesis. A rise in sterile inflammation occurs with ageing and the term "inflammaging" has been coined by to describe this phenomenon. This distinct form of sterile inflammation has an unknown role in in the pathogenesis of myeloid malignancies despite shared correlations with age and ageing-related diseases. More recent is a discovery that many cases of MDS arise from clonal hematopoiesis of indeterminate potential (CHIP), an age associated, asymptomatic pre-disease state. The interrelationship between ageing, inflammation and clonal CHIP is complex and likely bidirectional with causality between inflammaging and CHIP potentially instrumental to understanding MDS pathogenesis. Here we review the concept of inflammaging and MDS pathogenesis and explore their causal relationship by introducing a novel framing mechanism of "pre-clonal inflammaging" and "clonal inflammaging". We aim to harmonize research on ageing, inflammation and MDS pathogenesis by contextualizing the current understanding of inflammaging and the ageing hematopoietic system with what is known about the etiology of MDS via its progression from CHIP.

中文翻译：

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骨髓增生异常综合征的发病机制和炎症。


骨髓增生异常综合征 （MDS） 是一组遗传复杂且表型多样的克隆性血液系统肿瘤，随着年龄的增长而发生的频率越来越高。MDS 长期以来一直与全身性炎症有关，炎症信号紊乱与 MDS 发病机制有关。无菌性炎症的增加会随着年龄的增长而发生，因此创造了“炎症”一词来描述这种现象。这种独特形式的无菌性炎症在髓系恶性肿瘤的发病机制中的作用未知，尽管与年龄和衰老相关疾病具有共同的相关性。最近发现，许多 MDS 病例由不确定电位克隆造血 （CHIP） 引起，这是一种与年龄相关的无症状疾病前状态。衰老、炎症和克隆 CHIP 之间的相互关系很复杂，并且可能是双向的，炎症和 CHIP 之间的因果关系可能有助于理解 MDS 发病机制。在这里，我们回顾了炎症和 MDS 发病机制的概念，并通过引入“克隆前炎症”和“克隆炎症”的新框架机制来探讨它们的因果关系。我们的目标是通过将当前对炎症和衰老造血系统的理解与通过 CHIP 进展的 MDS 病因的已知信息联系起来，协调对衰老、炎症和 MDS 发病机制的研究。