Deciphering the Role of Microbially-driven Inflammation in Modulating DNMT3A-Deficient Leukemic Evolution

Hematopoietic stem cells (HSCs) regenerate blood but are prone to mutations that lead to myeloid malignancies. Mutations in DNMT3A, a hematopoietic cloning community of undetermined potential (CHIP), increase the risk of leukemia. Inflammation, particularly from microbial exposure, accelerates the spread of DNMT3A-mutant HSCs. Mouse models and human organoids will help elucidate the mechanisms of CHIP-AML progression, identifying early intervention and therapeutic strategies.