Franco Stephanie, Godley Lucy A
Department of Medicine, Northwestern Medicine, Chicago, IL, USA.
Division of Hematology/Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
J Exp Med. 2025 Jan 6;222(1). doi: 10.1084/jem.20230931. Epub 2024 Dec 3.
Somatic variants accumulate in all organs with age, with a positive selection of clonal populations that provide a fitness advantage during times of heightened cellular stress leading to clonal expansion. Easily measured within the hematopoietic compartment, clonal hematopoiesis (CH) is now recognized as a common process in which hematopoietic clones with somatic variants associated with hematopoietic neoplasms exist within the blood or bone marrow of individuals without evidence of malignancy. Most cases of CH involve a limited number of genes, most commonly DNMT3A, TET2, and ASXL1. CH confers risk for solid and hematopoietic malignancies as well as cardiovascular and numerous inflammatory diseases and offers opportunities for cancer prevention. Here, we explore the genetic and environmental factors that predispose individuals to CH with unique variant signatures and discuss how CH drives cancer progression with the goals of improving individual cancer risk stratification, identifying key intervention opportunities, and understanding how CH impacts therapeutic strategies and outcomes.
体细胞变异会随着年龄在所有器官中累积，在细胞应激增强导致克隆性扩张的时期，具有适应性优势的克隆群体受到正向选择。克隆性造血（CH）在造血系统中易于检测，目前被认为是一种常见现象，即在没有恶性肿瘤证据的个体的血液或骨髓中存在与造血肿瘤相关的体细胞变异的造血克隆。大多数CH病例涉及有限数量的基因，最常见的是DNMT3A、TET2和ASXL1。CH会增加患实体瘤和造血系统恶性肿瘤以及心血管疾病和多种炎症性疾病的风险，并为癌症预防提供机会。在此，我们探讨使个体易患具有独特变异特征的CH的遗传和环境因素，并讨论CH如何驱动癌症进展，目标是改善个体癌症风险分层、确定关键干预机会以及了解CH如何影响治疗策略和结果。
