Clonal hematopoiesis: Mutation-specific adaptation to environmental change

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 associ-ated with CHIP, such as old age, infections, chemotherapy, or cigarette smoking, alter tissue microenviron-ments 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.

Automated summary

Clonal hematopoiesis of indeterminate potential (CHIP) refers to the expansion of genetically variant hematopoietic cells, which increases with age and is associated with environmental factors such as infections, chemotherapy, and smoking. Understanding how these environmental contexts alter tissue microenvironments to facilitate the selection and expansion of specific CHIP mutant clones, as well as identifying remaining gaps in knowledge, will have implications for transplant and preventive medicine.