DDX41 haploinsufficiency causes inefficient hematopoiesis under stress and cooperates with p53 mutations to cause hematologic malignancy.

ABSTRACT: Germline heterozygous mutations in DDX41 predispose individuals to hematologic malignancies in adulthood. Most of these DDX41 mutations result in a truncated protein, leading to loss of protein function. To investigate the impact of these mutations on hematopoiesis, we generated mice with hematopoietic-specific knockout of one Ddx41 allele. Under normal steady-state conditions, there was minimal effect on lifelong hematopoiesis, resulting in a mild yet persistent reduction in red blood cell counts. However, stress induced by transplantation of the Ddx41^+/- BM resulted in hematopoietic stem/progenitor cell (HSPC) defects and onset of hematopoietic failure upon aging. Transcriptomic analysis of HSPC subsets from the transplanted BM revealed activation of cellular stress responses,

SUBMITTER: Stepanchick E 

PROVIDER: S-EPMC11286521 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature