Causes and Consequences of Clonal Hematopoiesis

Clonal hematopoiesis (CH) describes the outsized contribution of expanded clones of hematopoietic stem and progenitor cells (HSPCs) to blood cell production. The prevalence of CH increases dramatically with age. CH can be caused by somatic mutations in individual genes or by gains and or losses of larger chromosomal segments. CH is a premalignant state; the somatic mutations detected in CH are the initiating mutations for hematologic malignancies, and CH is a strong predictor for the development of blood cancers. Moreover, CH is associated with non-malignant disorders and increased overall mortality. The somatic mutations that drive clonal expansion of HSPCs can alter the function of terminally differentiated blood cells, including release of elevated levels of inflammatory cytokines. These cytokines may then contribute to a broad range of inflammatory disorders that increase in prevalence with age. Detection of specific somatic mutations in the peripheral blood, in coordination with blood count parameters, can powerfully predict the development of hematologic malignancies and overall mortality. In this review we summarize the current understanding of CH nosology and origins. We provide an overview of available tools for risk stratification and discuss management strategies for patients presenting to hematology clinics with CH.