Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Department of Haematology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom.
J Clin Invest. 2024 Oct 1;134(19):e180065. doi: 10.1172/JCI180065.
Clonal hematopoiesis (CH), the expansion of hematopoietic stem cells and their progeny driven by somatic mutations in leukemia-associated genes, is a common phenomenon that rises in prevalence with advancing age to affect most people older than 70 years. CH remains subclinical in most carriers, but, in a minority, it progresses to a myeloid neoplasm, such as acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasm. Over the last decade, advances in our understanding of CH, its molecular landscape, and the risks associated with different driver gene mutations have culminated in recent developments that allow for a more precise estimation of myeloid neoplasia risk in CH carriers. In turn, this is leading to the development of translational and clinical programs to intercept and prevent CH from developing into myeloid neoplasia. Here, we give an overview of the spectrum of CH driver mutations, what is known about their pathophysiology, and how this informs the risk of incident myeloid malignancy.
克隆性造血 (CH) 是指由白血病相关基因中的体细胞突变驱动的造血干细胞及其后代的扩增，是一种随着年龄增长而普遍发生的现象，影响大多数 70 岁以上的人。在大多数携带者中，CH 仍处于亚临床状态，但在少数情况下，它会进展为髓系肿瘤，如急性髓系白血病、骨髓增生异常综合征或骨髓增生性肿瘤。在过去的十年中，我们对 CH 的认识、其分子特征以及与不同驱动基因突变相关的风险取得了进展，最终实现了更精确地评估 CH 携带者中髓系肿瘤风险的新方法。反过来，这也导致了转化和临床计划的发展，以拦截和预防 CH 发展为髓系肿瘤。在这里，我们概述了 CH 驱动突变的范围、对其病理生理学的了解，以及这如何影响新发髓系恶性肿瘤的风险。
