Clonal hematopoiesis of indeterminate potential (CHIP) describes a widespread expansion of genetically variant hematopoietic cells that increases exponentially with age and is associated with increased risks of cancers, cardiovascular disease, and other maladies. Here, we discuss how environmental contexts associated with CHIP, such as old age, infections, chemotherapy, or cigarette smoking, alter tissue microenvironments to facilitate the selection and expansion of specific CHIP mutant clones. Further, we consider major remaining gaps in knowledge, including intrinsic effects, clone size thresholds, and factors affecting clonal competition, that will determine future application of this field in transplant and preventive medicine.

不确定潜力克隆造血 (CHIP) 描述了遗传变异造血细胞的广泛扩张，这种细胞随着年龄的增长呈指数增长，并与癌症、心血管疾病和其他疾病的风险增加相关。在这里，我们讨论与 CHIP 相关的环境背景（例如老年、感染、化疗或吸烟）如何改变组织微环境，以促进特定 CHIP 突变克隆的选择和扩增。此外，我们考虑了知识方面的主要空白，包括内在效应、克隆大小阈值和影响克隆竞争的因素，这将决定该领域在移植和预防医学中的未来应用。