Factors associated with clonal hematopoiesis and interaction with marrow environment

Clonal hematopoiesis (CH) is an expansion of clones in individuals without any hematologic abnormalities, often carrying the driver mutations implicated in myeloid tumors, such as DNMT3A, TET2, and ASXL1. Most notably, CH is an age-related event, accounting for ~ 10% of cases in people over 60 years old. CH may also be correlated with a previous history of cancer treatment with chemotherapeutic drugs/radiation and infection episodes. The link between aging and CH acquisition is best explained by the enhanced inflammatory level in the bone marrow environment, which in turn expands hematopoietic cell clones with mutations in myeloid drivers. This positive feedback accounts for not only increased incidence of subsequent myeloid tumors in CH carriers but also for increased all-cause mortality and cardiovascular diseases (CVD). Recent evidence from large-scale epidemiological studies with genetic profiles, and mice models that recapitulate hematopoietic clones harboring driver gene mutations has revealed the detailed pathophysiology of CH clones represented by specific driver mutations, especially regarding expansion mechanisms under environmental factors and how they alter the environment. This review introduces the current knowledge of CH with a special focus on its interaction with the marrow environment.