The origin of leukemia: genetic alterations and inflammatory factors in the development of pre-malignant clonal hematopoiesis

Abstract Clonal hematopoiesis of indetermined potential (CHIP) is increasingly common with age and identified in more than 1 in 10 healthy individuals at the age of 70. Mutations in epigenetic and splicing factors are recurrent genetic events in CHIP, and experimental data suggest that microbial and inflammatory factors may contribute to the selective expansion of hematopoietic stem cells carrying these mutations. In parallel, CHIP is associated with an increased incidence of cardiovascular disease and studies in mice support a causal relationship where mutated hematopoietic cells contribute to inflammation and atherosclerotic plaque formation. Collectively, current clinical and experimental data suggest a complex network where genetic alterations and inflammatory factors contribute to the development of the early stages of hematological malignancy.