Fedratinib and gandotinib induce apoptosis and enhance the efficacy of tyrosine kinase inhibitors in human mast cells.

ABSTRACT: Mastocytosis is characterized by an abnormal accumulation of mast cells (MC) in various organs. In most patients, the disease is driven by the KIT D816V mutation, leading to activation of the KIT receptor and subsequent downstream signaling, including the JAK/STAT pathway. In recent years, KIT-targeting tyrosine kinase inhibitors (TKI) have emerged for the treatment of systemic mastocytosis; however, the overall response rate is often not sufficient. In this study, we investigated whether targeting the JAK/STAT pathway might be a novel treatment approach in mastocytosis. Using human MC lines carrying the KIT D816V mutation and human primary cord blood-derived MC, we examined the effects of different JAK inhibitors. Our findings revealed that the JAK inhibitors fedratinib and

SUBMITTER: Makeeva A 

PROVIDER: S-EPMC11815366 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature