Kirschner Kristina, Kusne Yael, Cargo Catherine, Patnaik Mrinal M
Department Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, MN, USA; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Department of Hematology/Oncology, Mayo Clinic, Phoenix, AZ, USA.
Lancet Haematol. 2025 Aug;12(8):e650-e661. doi: 10.1016/S2352-3026(25)00137-1. Epub 2025 Jul 17.
Clonal haematopoiesis refers to the presence of somatic mutations in haematopoietic stem and progenitor cells, accompanied by the expansion of high-fitness clones over time. Age-related clonal haematopoiesis arises from ageing-related DNA damage and is associated with haematological neoplasms and coronary artery disease. Genotoxic therapies can promote the selection of somatic mutations, leading to therapy-related clonal haematopoiesis. Clonal haematopoiesis in acquired or inherited bone marrow failure syndromes and germline predispositions leads to clonal expansion, where fitness constraints on haematopoietic stem cells drive mutation acquisition. When clonal haematopoiesis occurs in the context of persistent unexplained cytopenias, with somatic mutations driving haematopoietic dysfunction, it is referred to as clonal cytopenias of undetermined significance (CCUS). CCUS is a precursor to myeloid neoplasms, with variable progression rates. In this Review, we summarise the current state of knowledge, offering critical insights into the molecular evolution of, and diagnostics and risk assessment for clonal haematopoiesis and CCUS. We highlight the interplay between ageing and environmental factors in the progression to haematological neoplasms and discuss challenges for risk stratification and disease monitoring.
克隆性造血是指造血干细胞和祖细胞中存在体细胞突变，并随着时间的推移伴有高适应性克隆的扩增。与年龄相关的克隆性造血源于与衰老相关的DNA损伤，与血液系统肿瘤和冠状动脉疾病相关。基因毒性疗法可促进体细胞突变的选择，导致治疗相关的克隆性造血。获得性或遗传性骨髓衰竭综合征以及种系易感性中的克隆性造血会导致克隆性扩增，其中造血干细胞的适应性限制会促使突变的发生。当克隆性造血发生在持续不明原因血细胞减少的情况下，且体细胞突变导致造血功能障碍时，称为意义未明的克隆性血细胞减少症（CCUS）。CCUS是髓系肿瘤的前驱病变，进展速度各异。在本综述中，我们总结了当前的知识状况，对克隆性造血和CCUS的分子演变、诊断及风险评估提供了重要见解。我们强调了衰老与环境因素在血液系统肿瘤进展中的相互作用，并讨论了风险分层和疾病监测面临的挑战。
