CHIP as a precursor state for hematological neoplasms. (A) A model for evolution from normal hematopoiesis to CHIP and then, in some cases, to MDS or AML. (B) Comparison of evolution patterns of MGUS, MBL, and CHIP. Hematopoietic progenitor 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. Although this article primarily discusses CHIP in the context of its distinction from MDS, 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. Just as with MGUS and MBL, the majority of patients with CHIP will never develop an overt neoplasm, and patients will eventually die of unrelated causes.