Age-related micro-environmental changes as drivers of clonal hematopoiesis

Tal Bacharach, Nathali Kaushansky, Liran I. Shlush*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)

Abstract

Purpose of reviewBoth aging and reduced diversity at the hematopoietic stem cells (HSCs) level are ubiquitous. What remains unclear is why some individuals develop clonal hematopoiesis (CH), and why does CH due to specific mutations occur in specific individuals. Much like aging, reduced diversity of HSCs is a complex phenotype shaped by numerous factors (germline & environment). The purpose of the current review is to discuss the role of two other age-related ubiquitous processes that might contribute to the dynamics and characteristics of losing HSC diversity and the evolution of CH. These processes have not been reviewed in depth so far and include the accumulation of fatty bone marrow (FBM), and the decline in sex hormones.Recent findingsInterestingly, sex hormone decline can directly shape HSC function, but also reshape the delicate balance of BM supporting cells, with a shift towards FBM. FBM accumulation can shape the clonal expansion of preleukemic mutations, particularly DNMT3A mutations, through IL-6 mediation. DNMT3A mutations are one of the only preleukemic mutations which is more prevalent in women, and especially in women with early menopause, demonstrating an association between age-related hormone decline and CH evolution, the mechanisms of which are yet to be discovered.SummaryAging is a multifactorial phenotype and the same is true for the aging of the blood system. While many factors which can shape CH have been discussed, we shed more light on FBM and sex hormone decline.

Original languageEnglish
Pages (from-to)53-57
Number of pages5
JournalCurrent Opinion in Hematology
Volume31
Issue number2
DOIs
Publication statusPublished - 1 Mar 2024

Funding

Publisher Copyright: © 2024 Lippincott Williams and Wilkins. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Hematology

Fingerprint

Dive into the research topics of 'Age-related micro-environmental changes as drivers of clonal hematopoiesis'. Together they form a unique fingerprint.

Cite this