Dysregulated innate immune signaling cooperates with RUNX1 mutations to transform an MDS-like disease to AML.

ABSTRACT: Dysregulated innate immune signaling is linked to preleukemic conditions and myeloid malignancies. However, it is unknown whether sustained innate immune signaling contributes to malignant transformation. Here we show that cell-intrinsic innate immune signaling driven by miR-146a deletion (miR-146a^KO), a commonly deleted gene in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), cooperates with mutant RUNX1 (RUNX1^mut) to initially induce marrow failure and features of MDS. However, miR-146a^KO hematopoietic stem and/or progenitor cells (HSPCs) expressing RUNX1^mut eventually progress to a fatal AML. miR-146a^KO HSPCs exhaust during serial transplantation, while expression of RUNX1^mut restored their hematopoietic

SUBMITTER: Barreyro L 

PROVIDER: S-EPMC11112336 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature