Dana-Farber/Boston Children's Hospital Cancer and Blood Disorders Center, Boston, MA, USA.
Boston Children's Hospital, Boston, MA 02215, USA; Howard Hughes Medical Institute, USA.
Trends Cell Biol. 2023 Aug;33(8):695-707. doi: 10.1016/j.tcb.2022.12.001. Epub 2022 Dec 31.
Acquired genetic or cytogenetic alterations in a blood stem cell that confer clonal fitness promote its relative expansion leading to clonal hematopoiesis (CH). Despite a largely intact hematopoietic output, CH is associated with a heightened risk of progression to hematologic malignancies and with non-hematologic health manifestations, including cardiovascular disease and overall mortality. We focus on the evidence for the role of inflammation in establishing, maintaining and reciprocally being affected by CH. We describe the known pro-inflammatory signals associated with CH and preclinical studies that elucidated the cellular mechanisms involved. We review the evolving literature on early-onset CH in germline predisposition conditions and the possible role of immune dysregulation in this context.
在造血干细胞中获得的遗传或细胞遗传学改变，赋予其克隆适应性，促进其相对扩张，从而导致克隆性造血（CH）。尽管造血输出基本完好，但 CH 与向血液系统恶性肿瘤发展的风险增加以及非血液系统健康表现（包括心血管疾病和总体死亡率）相关。我们重点关注炎症在建立、维持和相互影响 CH 方面的作用的证据。我们描述了与 CH 相关的已知促炎信号以及阐明相关细胞机制的临床前研究。我们回顾了关于种系易感性疾病中早发性 CH 的不断发展的文献，以及免疫失调在这方面的可能作用。
