Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA; email:
Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Annu Rev Genomics Hum Genet. 2024 Aug;25(1):329-351. doi: 10.1146/annurev-genom-120722-100409.
Clonal hematopoiesis (CH) is an age-related process whereby hematopoietic stem and progenitor cells (HSPCs) acquire mutations that lead to a proliferative advantage and clonal expansion. The most commonly mutated genes are epigenetic regulators, DNA damage response genes, and splicing factors, which are essential to maintain functional HSPCs and are frequently involved in the development of hematologic malignancies. Established risk factors for CH, including age, prior cytotoxic therapy, and smoking, increase the risk of acquiring CH and/or may increase CH fitness. CH has emerged as a novel risk factor in many age-related diseases, such as hematologic malignancies, cardiovascular disease, diabetes, and autoimmune disorders, among others. Future characterization of the mechanisms driving CH evolution will be critical to develop preventative and therapeutic approaches.
克隆性造血 (CH) 是一种与年龄相关的过程，其中造血干细胞和祖细胞 (HSPCs) 获得导致增殖优势和克隆扩增的突变。最常见的突变基因是表观遗传调节剂、DNA 损伤反应基因和剪接因子，它们对于维持功能性 HSPCs 至关重要，并且经常参与血液系统恶性肿瘤的发生。CH 的既定危险因素，包括年龄、先前的细胞毒性治疗和吸烟，增加了获得 CH 和/或可能增加 CH 适应性的风险。CH 已成为许多与年龄相关的疾病的新危险因素，例如血液系统恶性肿瘤、心血管疾病、糖尿病和自身免疫性疾病等。未来对驱动 CH 进化的机制的特征描述对于开发预防和治疗方法至关重要。
