Dual ASXL1 and CSF3R mutations drive myeloid-biased stem cell expansion and enhance neutrophil differentiation.

ABSTRACT:

Abstract

Mutations in the epigenetic regulator Additional Sex Combs-Like 1 (ASXL1) are frequently observed in chronic neutrophilic leukemia (CNL). CNL is a myeloproliferative neoplasm (MPN) driven by activating mutations in the Colony Stimulating Factor 3 Receptor (CSF3R), which cause excessive neutrophil production. Despite the high rates of co-occurrence, the interplay between ASXL1 and CSF3R mutations in hematopoiesis and leukemia remains poorly understood. Here, we present a new mouse model with both Asxl1Y588X and Csf3rT621I mutations, which recapitulates features of human MPNs. Csf3r-mutant mice exhibit an age-associated depletion of hematopoietic stem cells, which is tempered by adding Asxl1Y588X. This combination of mutations causes an expansion of myeloid-biased long-term

SUBMITTER: Darmusey L 

PROVIDER: S-EPMC11986226 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature