Activation of targetable inflammatory immune signaling is seen in myelodysplastic syndromes with SF3B1 mutations.

ABSTRACT:

Background

Mutations in the SF3B1 splicing factor are commonly seen in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), yet the specific oncogenic pathways activated by mis-splicing have not been fully elucidated. Inflammatory immune pathways have been shown to play roles in the pathogenesis of MDS, though the exact mechanisms of their activation in splicing mutant cases are not well understood.

Methods

RNA-seq data from SF3B1 mutant samples was analyzed and functional roles of interleukin-1 receptor-associated kinase 4 (IRAK4) isoforms were determined. Efficacy of IRAK4 inhibition was evaluated in preclinical models of MDS/AML.

Results

RNA-seq splicing analysis of SF3B1 mutant MDS samples revealed retention of full-

SUBMITTER: Choudhary GS 

PROVIDER: S-EPMC9427103 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature