Clonal hematopoiesis (CH) defines a premalignant state predominantly found in older persons that increases the risk of developing hematologic malignancies and age-related inflammatory diseases. However, the risk for malignant transformation or non-malignant disorders is variable and difficult to predict, and defining the clinical relevance of specific candidate driver mutations in individual carriers has proved to be challenging. In addition to the cell-intrinsic mechanisms, mutant cells rely on and alter cell-extrinsic factors from the bone marrow (BM) niche, which complicates the prediction of a mutant cell’s fate in a shifting pre-malignant microenvironment. Therefore, identifying the insidious and potentially broad impact of driver mutations on supportive niches and immune function in CH aims to understand the subtle differences that enable driver mutations to yield different clinical outcomes. Here, we review the changes in the aging BM niche and the emerging evidence supporting the concept that CH can progressively alter components of the local BM microenvironment. These alterations may have profound implications for the functionality of the osteo-hematopoietic niche and overall bone health, consequently fostering a conducive environment for the continued development and progression of CH. We also provide an overview of the latest technology developments to study the spatiotemporal dependencies in the CH BM niche, ideally in the context of longitudinal studies following CH over time. Finally, we discuss aspects of CH carrier management in clinical practice, based on work from our group and others.

克隆造血（CH）是一种主要见于老年人的癌前状态，会增加患血液系统恶性肿瘤和与年龄相关的炎症性疾病的风险。然而，恶性转化或非恶性疾病的风险是可变的且难以预测，并且确定个体携带者中特定候选驱动突变的临床相关性已被证明是具有挑战性的。除了细胞内在机制之外，突变细胞还依赖并改变来自骨髓（BM）生态位的细胞外在因素，这使得突变细胞在不断变化的癌前微环境中的命运预测变得复杂。因此，确定驱动突变对 CH 的支持性生态位和免疫功能的潜在和潜在广泛影响，旨在了解驱动突变产生不同临床结果的微妙差异。在这里，我们回顾了老化 BM 生态位的变化以及支持 CH 可以逐渐改变局部 BM 微环境组成部分这一概念的新证据。这些改变可能对骨造血生态位的功能和整体骨骼健康产生深远的影响，从而为 CH 的持续发展和进展创造有利的环境。我们还概述了最新的技术发展，以研究 CH BM 利基中的时空依赖性，最好是在 CH 随着时间的推移进行的纵向研究的背景下。最后，我们根据我们小组和其他人的工作，讨论临床实践中 CH 携带者管理的各个方面。