An inflammatory T-cell-stromal axis contributes to hematopoietic stem/progenitor cell failure and clonal evolution in human myelodysplastic syndrome.

ABSTRACT: Myelodysplastic syndrome (MDS) is characterized by bone marrow failure, clonal evolution and leukemic progression, but the pathophysiologic processes driving these events remain incompletely understood. Here, by establishing a comprehensive single-cell transcriptional taxonomy of human MDS, we reveal that inflammatory remodeling of bone marrow stromal niches is a common early feature, irrespective of the genetic driver landscape. We identify an activated CD8-T-cell subset as a source of stromal inflammation via TNF-receptor signaling, which prompts the inflammatory rewiring and loss of repopulating ability of residual normal hematopoietic stem/progenitor cells (HSPC). Mutant HSPCs display relative resistance to this inflammatory stress and reside predominantly in a transcriptional 'high ou

SUBMITTER: Chen L 

PROVIDER: S-EPMC12627551 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature