The Origin of Clonal Hematopoiesis and Its Implication in Human Diseases

Clonal expansion of hematopoietic cells is first observed in hematological malignancies where all the leukemic cells can be traced back to a single cell carrying oncogenic alterations. Interestingly, expansion of hematopoietic clones with defined genomic alterations, including single nucleotide variants (SNVs), small insertions and deletions (indels), and large structural chromosomal alterations (CAs), is also found in the healthy population. These genomic changes often affect leukemia driver genes. As a result, healthy individuals bearing such clonal hematopoiesis (CH) are at a higher risk of hematological malignancies. In addition to blood cancers, SNV/indel-related CH has been found associated with elevated cardiovascular and all-cause mortality, indicating adverse impacts of abnormalities in the blood on the normal functions of non-hematological tissues. In the past decade, much effort has been invested in understanding the origins of CH and its causal relationship with diseases in hematological and non-hematological tissues. Here, we review recent progress in these areas and discuss future directions that can be pursued to translate the acquired knowledge into better management of CH-related diseases.