Targeting the CD74 signaling axis suppresses inflammation and rescues defective hematopoiesis in <i>RUNX1</i>-familial platelet disorder.

ABSTRACT: Familial platelet disorder (FPD) is associated with germline RUNX1 mutations, establishing a preleukemic state and increasing the risk of developing leukemia. Currently, there are no intervention strategies to prevent leukemia progression. Single-cell RNA sequencing (n = 10) combined with functional analysis of samples from patients with RUNX1-FPD (n > 75) revealed that FPD hematopoietic stem and progenitor cells (HSPCs) displayed increased myeloid differentiation and suppressed megakaryopoiesis because of increased activation of prosurvival and inflammatory pathways. Bone marrow from patients with RUNX1-FPD contained an elevated cytokine milieu, exerting chronic inflammatory stress on HSPCs. RUNX1-FPD HSPCs were myeloid biased, had increased self-

SUBMITTER: Mohammadhosseini M 

PROVIDER: S-EPMC11912227 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature