Clonal hematopoiesis of indeterminate potential: clinical relevance of an incidental finding in liquid profiling

Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is a hematologic precursor lesion that is defined by the presence of somatic mutations in peripheral blood cells but without evidence for the presence of leukemia or another hematologic neoplasm. CHIP is frequent in elderly individuals and can be detected as incidental finding in liquid profiling of cell-free DNA. While liquid profiling assays aim to reduce the biological noise generated by CHIP and to discriminate solid cancer-associated from CHIP-associated mutation profiles, the finding of CHIP is of potential clinical relevance at its own. Overall, CHIP is associated with a moderate risk of progression to an overt hematologic neoplasm of 1% per year. The risk increases substantially in patients with unexplained blood count abnormalities, multiple mutations, or specific patterns of mutations. In patients with solid cancer, the presence of CHIP increases the risk for development of treatment-related myeloid neoplasms. In addition, CHIP has been associated with a number of non-hematological diseases and represents a previously unrecognized major risk factor for cardiovascular disease. The management of individuals diagnosed with CHIP includes both hematologic and cardiovascular risk assessment in a multidisciplinary setting. Additional evidence from interventional studies is needed to integrate CHIP into a personalized treatment approach for patients with solid cancer.