不确定潜能的克隆性造血与衰老

Clonal hematopoiesis of indeterminate potential and aging

近年来将非血液系统恶性肿瘤患者外周血可检测突变体细胞比例>2%定义为不确定潜能的克隆性造血(CHIP)。CHIP可以通过改变DNA损伤应答、改变转录程序、改变表观遗传学等增加恶性疾病的患病风险,显著升高携带者血液系统恶性肿瘤的发病率。除此之外,CHIP代表了一种与衰老相关的新型危险因素。近期研究显示,CHIP携带者感染、贫血、心力衰竭、血栓事件、血液系统肿瘤等疾病发生率均显著升高。本文从研究CHIP相关基因突变表观遗传学修饰、表型改变及炎症机制入手,讨论CHIP增加衰老相关疾病的发病机制及可能的干预措施。

Clonal hematopoiesis with indeterminant potential(CHIP)is defined as the proportion of detectable clonal hematopoietic cells in peripheral blood exceeding 2%and without confirmed hematologic malignancy.CHIP could increase the risk of malignant diseases through changes in DNA damage response,transcriptional programming and epigenetic modification.The incidence of malignant tumors in the blood system is significantly higher in the CHIP patients than healthy person.In addition,CHIP represents a negative factor associated with aging.Recent studies have found that the incidences of infections,anemia,heart failure,thrombotic events,and tumors of the blood system in CHIP carriers were significantly increased.Starting with the epigenetic modifications,phenotypic changes and inflammatory mechanisms of CHIP-related gene mutations,this paper discussed the mechanisms of CHIP-related diseases and possible intervention aimed at aging.