Genetic and environmental risks for clonal hematopoiesis and cancer

Stephanie Franco, Lucy A. Godley*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Somatic variants accumulate in all organs with age, with a positive selection of clonal populations that provide a fitness advantage during times of heightened cellular stress leading to clonal expansion. Easily measured within the hematopoietic compartment, clonal hematopoiesis (CH) is now recognized as a common process in which hematopoietic clones with somatic variants associated with hematopoietic neoplasms exist within the blood or bone marrow of individuals without evidence of malignancy. Most cases of CH involve a limited number of genes, most commonly DNMT3A, TET2, and ASXL1. CH confers risk for solid and hematopoietic malignancies as well as cardiovascular and numerous inflammatory diseases and offers opportunities for cancer prevention. Here, we explore the genetic and environmental factors that predispose individuals to CH with unique variant signatures and discuss how CH drives cancer progression with the goals of improving individual cancer risk stratification, identifying key intervention opportunities, and understanding how CH impacts therapeutic strategies and outcomes.

Original languageEnglish (US)
Article numbere20230931
JournalJournal of Experimental Medicine
Volume222
Issue number1
DOIs
StatePublished - Jan 6 2025

Keywords

  • Cancer Focus
  • Hematopoiesis
  • Human disease genetics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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