Clonal hematopoiesis: mechanisms driving dominance of stem cell clones

Blood. 2020 Oct 1;136(14):1590-1598. doi: 10.1182/blood.2020006510.


The discovery of clonal hematopoiesis (CH) in older individuals has changed the way hematologists and stem cell biologists view aging. Somatic mutations accumulate in stem cells over time. While most mutations have no impact, some result in subtle functional differences that ultimately manifest in distinct stem cell behaviors. With a large pool of stem cells and many decades to compete, some of these differences confer advantages under specific contexts. Approximately 20 genes are recurrently found as mutated in CH, indicating they confer some advantage. The impact of these mutations has begun to be analyzed at a molecular level by modeling in cell lines and in mice. Mutations in epigenetic regulators such as DNMT3A and TET2 confer an advantage by enhancing self-renewal of stem and progenitor cells and inhibiting their differentiation. Mutations in other genes involved in the DNA damage response may simply enhance cell survival. Here, we review proposed mechanisms that lead to CH, specifically in the context of stem cell biology, based on our current understanding of the function of some of the CH-associated genes.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Cell Differentiation / genetics
  • Clonal Evolution / genetics
  • Clonal Hematopoiesis* / genetics
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Damage
  • DNA Methyltransferase 3A
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dioxygenases
  • Discoidin Domain Receptors / genetics
  • Discoidin Domain Receptors / metabolism
  • Gene Expression Regulation, Developmental
  • Hematopoiesis* / genetics
  • Humans
  • Mutation
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Stem Cells / cytology*
  • Stem Cells / metabolism*


  • Biomarkers
  • DNA-Binding Proteins
  • DNMT3A protein, human
  • Dnmt3a protein, mouse
  • Proto-Oncogene Proteins
  • Dioxygenases
  • TET2 protein, human
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • Discoidin Domain Receptors