Clonal hematopoiesis (CH), the relative expansion of mutant clones, is derived from hematopoietic stem cells (HSCs) with acquired somatic or cytogenetic alterations that improve cellular fitness. Individuals with CH have a higher risk for hematological and non-hematological diseases, such as cardiovascular disease, and have an overall higher mortality rate. Originally thought to be restricted to a small fraction of elderly people, recent advances in single-cell sequencing and bioinformatics have revealed that CH with multiple expanded mutant clones is universal in the elderly population. Just a few years ago, phylogenetic reconstruction across the human lifespan and novel sensitive sequencing techniques showed that CH can start earlier in life, decades before it was thought possible. These studies also suggest that environmental factors acting through aberrant inflammation might be a common theme promoting clonal expansion and disease progression. However, numerous aspects of this phenomenon remain to be elucidated and the precise mechanisms, context-specific drivers, and pathways of clonal expansion remain to be established. Here, we review our current understanding of the cellular mechanisms driving CH and specifically focus on how pro-inflammatory factors affect normal and mutant HSC fates to promote clonal selection.
克隆造血（CH）是指突变克隆的相对扩增，源于造血干细胞（HSC）获得性体细胞或细胞遗传学改变，这些改变提升了细胞的适应性。携带克隆造血的个体罹患血液系统疾病和非血液系统疾病（如心血管疾病）的风险更高，总体死亡率也更高。过去曾认为克隆造血仅局限于少数老年人，但近年来单细胞测序和生物信息学技术的进展揭示，携带多个扩增突变克隆的克隆造血现象在老年群体中普遍存在。就在几年前，通过人类生命周期系统发育重建及新型高灵敏度测序技术研究发现，克隆造血可能始于生命更早期，比既往认知提前数十年。这些研究还提示，通过异常炎症发挥作用的环境因素可能是促进克隆扩增和疾病进展的共同诱因。然而，该现象的诸多方面仍有待阐明，克隆扩增的具体机制、环境特异性驱动因素及作用通路尚未完全明确。本文综述了当前对驱动克隆造血的细胞机制的理解，特别聚焦于促炎因子如何影响正常及突变造血干细胞的命运，从而促进克隆选择。
Decoding Clonal Hematopoiesis: Emerging Themes and Novel Mechanistic Insights
肿瘤(癌症)患者之家