Abstract Body

Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-associated condition in individuals who do not have a hematologic malignancy or altered blood counts. CHIP is defined by the presence of clonal, somatic mutations that are found in myeloid malignancies. These mutations are commonly the initiating events for myeloid malignancies, and CHIP is associated with a striking increased risk of hematologic malignancy. Analysis of large cohort studies has revealed that CHIP is also associated with a range of inflammatory disorders as well as solid tumor development. In murine models, Tet2 inactivation in blood cells leads to amplified responses to inflammatory stimuli, acceleration of atherosclerosis, and exacerbation of other disease processes. Clonal hematopoiesis is revealing insights into the initiation of hematologic malignancies, the biology of clonal selection, and the broad consequences of somatic mutations on the function of terminally differentiated blood cells.