A heterozygous CEBPA mutation disrupting the bZIP domain in a RUNX1 and SRSF2 mutational background causes MDS disease progression.

ABSTRACT: Myelodysplastic syndrome disease (MDS) is caused by the successive acquisition of mutations and thus displays a variable risk for progression to AML. Mutations in CEBPA are commonly associated with a high risk of disease progression, but whether they are causative for AML development is unclear. To analyse the molecular basis of disease progression we generated MDS patient-derived induced pluripotent stem cells from a low risk male patient harbouring RUNX1/SRSF2 mutations. This experimental model faithfully recapitulates the patient disease phenotypes upon hematopoietic differentiation. Introduction of a frameshift mutation affecting the C/EBPα bZIP domain in cells from low-risk stages mimicks disease progression by reducing clonogenicity of myeloid cells, blocking granulopoiesis and incre

SUBMITTER: Almaghrabi R 

PROVIDER: S-EPMC12219322 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature