TKI-mediated inhibition of NLRP1 inflammasome restores erythropoiesis in DBA syndrome.

ABSTRACT: Diamond-Blackfan anemia syndrome (DBAS) is marked by defective erythropoiesis caused by impaired ribosome biogenesis and aberrant signaling. Here, we investigate how ribosomal stress-induced activation of the NLRP1 inflammasome affects erythroid differentiation in DBAS. We demonstrate that FDA/EMA-approved tyrosine kinase inhibitors (TKIs) effectively mitigate defective erythropoiesis by inhibiting NLRP1 inflammasome activation. In K562 cells, nilotinib suppresses the ZAKα/P38/NLRP1/CASP1 axis, leading to increased GATA1 levels and upregulation of key erythroid genes. These effects were validated in human CD34⁺ hematopoietic stem and progenitor cells (HSPCs) and zebrafish models, where nilotinib, imatinib, and dasatinib promoted erythropoiesis while reducing caspase-1 activity. In Rps19-de

SUBMITTER: Lozano-Gil JM 

PROVIDER: S-EPMC12905221 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature