Clonal hematopoiesis: Molecular basis and clinical relevance.

Recent genomics studies have revealed that clonal hematopoietic expansion due to recurrent somatic mutations in hematopoietic cells are common in older people without evidence of hematological malignancies. This phenomenon, termed clonal hematopoiesis of indeterminate potential (CHIP), is associated with greater risk for hematological malignancy and cardiovascular diseases, leading to decreased overall survival of the affected individuals. The most frequently mutated genes in CHIP cases include genes associated with epigenetic modification, cell signaling, DNA damage response and RNA splicing, which are all recurrently mutated in myeloid malignancies. Recent findings suggest that these genetic alleles exert pleiotropic effects on hematopoietic stem cell (HSC) functions, transcriptional regulations, DNA damage responses and resistance to cellular stresses. Recent studies have uncovered the clinical relevance of CHIP in various settings during the management of hematological malignancies. Elucidating overall picture of clonal evolution based on CHIP will help developing preventive measures and novel treatments for hematological malignancies.