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CHIP: a clonal odyssey of the bone marrow niche
Wolfgang E. Schleicher, … , James DeGregori, Eric M. Pietras
Wolfgang E. Schleicher, … , James DeGregori, Eric M. Pietras
Published August 1, 2024
Citation Information: J Clin Invest. 2024;134(15):e180068. https://doi.org/10.1172/JCI180068.
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Review Series

CHIP: a clonal odyssey of the bone marrow niche

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Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the selective expansion of hematopoietic stem and progenitor cells (HSPCs) carrying somatic mutations. While CHIP is typically asymptomatic, it has garnered substantial attention due to its association with the pathogenesis of multiple disease conditions, including cardiovascular disease (CVD) and hematological malignancies. In this Review, we will discuss seminal and recent studies that have advanced our understanding of mechanisms that drive selection for mutant HSPCs in the BM niche. Next, we will address recent studies evaluating potential relationships between the clonal dynamics of CHIP and hematopoietic development across the lifespan. Next, we will examine the roles of systemic factors that can influence hematopoietic stem cell (HSC) fitness, including inflammation, and exposures to cytotoxic agents in driving selection for CHIP clones. Furthermore, we will consider how — through their impact on the BM niche — lifestyle factors, including diet, exercise, and psychosocial stressors, might contribute to the process of somatic evolution in the BM that culminates in CHIP. Finally, we will review the role of old age as a major driver of selection in CHIP.

Authors

Wolfgang E. Schleicher, Bridget Hoag, Marco De Dominici, James DeGregori, Eric M. Pietras

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Figure 1

Changes to the BM niche with aging, metabolic imbalance, and/or chronic stress can promote CHIP.

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Changes to the BM niche with aging, metabolic imbalance, and/or chronic ...
The BM niche is composed of multiple cell types that support long-term HSC function. Aging, metabolic imbalance, and chronic stress can result in changes to the BM niche that impair HSPC fitness in a way that could lead to the selection for mutant HSPCs and the eventual clonal outgrowth of mature blood cells associated with CHIP. This includes changes to the MSCs and increased inflammation and adipose tissue, together with reduced BM mineral density. Other changes with aging that are not depicted here include the loss of osteolineage cells, reduced innate and adaptive immunity, and phenotypic changes in HSPCs and their more mature progeny.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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