Metformin reduces the competitive advantage of Dnmt3a^R878H HSPCs.

ABSTRACT: Clonal haematopoiesis arises when a haematopoietic stem cell (HSC) acquires a mutation that confers a competitive advantage over wild-type HSCs, resulting in its clonal expansion. Individuals with clonal haematopoiesis are at increased risk of developing haematologic neoplasms and other age-related inflammatory illnesses^1-4. Suppressing the expansion of mutant HSCs may prevent these outcomes; however, such interventions have not yet been identified. The most common clonal haematopoiesis driver mutations are in the DNMT3A gene, with arginine 882 (R882) being a mutation hotspot^1-3,5-7. Here we show that mouse haematopoietic stem and progenitor cells (HSPCs) carrying the Dnmt3a^R878H/+ mutation, equivalent to human DNMT3A^R882H/+, have increased mitoc

SUBMITTER: Hosseini M 

PROVIDER: S-EPMC12869297 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature