Outgrowth of a mutated hematopoietic stem/progenitor clone and its descendants, also known as clonal hematopoiesis, has long been considered as either a potential forerunner to hematologic malignancy or as a clinically silent phase in leukemia that antedates symptomatic disease. That definition of clonal hematopoiesis has now been expanded to encompass patients who harbor specific genetic/epigenetic mutations that lead to clonal hematopoiesis of indeterminate potential (CHIP) and, with it, a relatively heightened risk for both myeloid malignancy and atherosclerosis during aging. In this review, we provide contemporary insights into the cellular and molecular basis for CHIP and explore the relationship of CHIP to myeloid malignancy and atherosclerosis. We also discuss emerging strategies to explore CHIP biology and clinical targeting of CHIP related malignancy and cardiovascular disease.
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