Chiba Shigeru
Division of Stem Cell Therapy, Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Division of Hematology, Mito Saiseikai General Hospital, Mito, Ibaraki, Japan.
Int J Hematol. 2025 Jul 31. doi: 10.1007/s12185-025-04034-9.
Clonal hematopoiesis (CH) has emerged as a common age-related phenomenon and a central concept linking somatic mutations in hematopoietic stem cells to both malignant and non-malignant diseases. While initially recognized in the context of hematologic neoplasms, CH is now known to contribute to increased all-cause mortality, particularly through heightened risk of cardiovascular and inflammatory diseases. Frequent mutations in genes such as DNMT3A, TET2, and ASXL1 alter epigenetic regulation and immune signaling, thereby promoting clonal expansion and systemic consequences. Longitudinal studies have illuminated the dynamics of clonal growth and revealed how germline variants influence somatic selection. VEXAS syndrome, driven by UBA1-mutated CH, exemplifies the broader clinical reach of clonal expansion beyond malignancy. CH occupies an intermediate biological state with far-reaching implications. In this Progress in Hematology series, contributors explore the natural history, genetic underpinnings, and inflammatory manifestations of CH, offering insights into its role as both a biomarker and a potential therapeutic target in aging populations.
克隆性造血（CH）已成为一种常见的与年龄相关的现象，是一个将造血干细胞中的体细胞突变与恶性和非恶性疾病联系起来的核心概念。虽然CH最初是在血液肿瘤的背景下被认识到的，但现在已知它会导致全因死亡率增加，特别是通过增加心血管疾病和炎症性疾病的风险。DNMT3A、TET2和ASXL1等基因的频繁突变会改变表观遗传调控和免疫信号传导，从而促进克隆性扩增和全身性后果。纵向研究阐明了克隆性生长的动态过程，并揭示了种系变异如何影响体细胞选择。由UBA1突变的CH驱动的VEXAS综合征例证了克隆性扩增在恶性肿瘤之外更广泛的临床影响。CH处于一种具有深远影响的中间生物学状态。在这个血液学进展系列中，撰稿人探讨了CH的自然史、遗传基础和炎症表现，深入了解其作为衰老人群中的生物标志物和潜在治疗靶点的作用。
