A Model of Clonal Expansion and Clonal Evolution From Normal Hematopoeisis to Myelodysplasia and Myeloid Leukemia. Clonal hematopoiesis of indeterminate potential (CHIP) as a precursor state for hematologic neoplasms. The figure depicts a model for evolution from normal hematopoiesis to CHIP and then, in some cases, to myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Hematopoietic progenitor cells or stem cells commonly acquire mutations throughout the human lifespan; most of these are passenger mutations that have no consequence for hematopoiesis. Certain mutations, however, confer a survival advantage to the mutated cell and its progeny and allow clonal expansion. Serial acquisition of mutations in an expanded clone can lead to a disease phenotype and ultimately, morbidity and mortality. CHIP can also directly progress to AML without an intervening MDS stage, and CHIP can progress to other conditions such as myeloproliferative neoplasms or lymphoid neoplasms. The majority of patients with CHIP will never develop an overt neoplasm, and patients will eventually die of unrelated causes.From Steensma et al. Blood. 2015;126:9-16, with permission.