BRAF inhibitors enhance erythropoiesis and treat anemia through paradoxical activation of MAPK signaling.

ABSTRACT: Erythropoiesis is a crucial process in hematopoiesis, yet it remains highly susceptible to disruption by various diseases, which significantly contribute to the global challenges of anemia and blood shortages. Current treatments like erythropoietin (EPO) or glucocorticoids often fall short, especially for hereditary anemias such as Diamond-Blackfan anemia (DBA). To uncover new erythropoiesis-stimulating agents, we devised a screening system using primary human hematopoietic stem and progenitor cells (HSPCs). We discovered that BRAF inhibitors (BRAFi), commonly used to treat BRAF^V600E melanoma, can unexpectedly and effectively promote progenitor cell proliferation by temporarily delaying erythroid differentiation. Notably, these inhibitors exhibited pronounced efficacy even under

SUBMITTER: Wu S 

PROVIDER: S-EPMC11609275 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature