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Updated: Jun 18, 2025

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CHIP: a clonal odyssey of the bone marrow niche

Wolfgang E Schleicher1, Bridget Hoag2, Marco De Dominici2

  • 1Division of Hematology, Department of Medicine, and.

The Journal of Clinical Investigation
|August 1, 2024
PubMed

Insights

Clonal hematopoiesis of indeterminate potential (CHIP) involves stem cell mutations. This review explores factors driving CHIP, including aging, inflammation, and lifestyle, linking it to diseases like cardiovascular disease and blood cancers.

Area of Science:

  • Hematology
  • Genetics
  • Aging Research

Background:

  • Clonal hematopoiesis of indeterminate potential (CHIP) is defined by somatic mutations in hematopoietic stem and progenitor cells (HSPCs).
  • CHIP is linked to increased risks of cardiovascular disease (CVD) and hematological malignancies.
  • Understanding CHIP mechanisms is crucial for early detection and intervention.

Purpose of the Study:

  • To review mechanisms driving mutant HSPC selection in the bone marrow (BM) niche.
  • To examine clonal dynamics of CHIP across the lifespan.
  • To explore systemic and lifestyle factors influencing CHIP development.

Main Methods:

  • Review of seminal and recent studies on CHIP.
  • Analysis of factors influencing hematopoietic stem cell (HSC) fitness.
  • Examination of the bone marrow niche and somatic evolution.

Main Results:

  • Mutant HSPC expansion is driven by BM niche selection.
  • CHIP clonal dynamics interact with hematopoietic development.
  • Systemic factors (inflammation, cytotoxic agents) and lifestyle (diet, exercise, stress) influence CHIP.
  • Old age is a significant driver of CHIP selection.

Conclusions:

  • CHIP pathogenesis is multifactorial, involving genetic, environmental, and age-related factors.
  • Somatic evolution in the BM niche culminates in CHIP.
  • Further research is needed to elucidate CHIP's role in disease progression.

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