Metformin reduces the clonal fitness of <i>Dnmt3a</i> ^R878H hematopoietic stem and progenitor cells by reversing their aberrant metabolic and epigenetic state.

ABSTRACT: Clonal hematopoiesis (CH) arises when a hematopoietic stem cell (HSC) acquires a mutation that confers a competitive advantage over wild-type (WT) HSCs, resulting in its clonal expansion. Individuals with CH are at an increased risk of developing hematologic neoplasms and a range of age-related inflammatory illnesses^1-3. Therapeutic interventions that suppress the expansion of mutant HSCs have the potential to prevent these CH-related illnesses; however, such interventions have not yet been identified. The most common CH driver mutations are in the DNA methyltransferase 3 alpha (DNMT3A) gene with arginine 882 (R882) being a mutation hotspot. Here we show that murine hematopoietic stem and progenitor cells (HSPCs) carrying the Dnmt3a ^R878H/+ mutation, whi

SUBMITTER: Hosseini M 

PROVIDER: S-EPMC10889081 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature