Myeloproliferative neoplasms (MPN) are hematological disorders driven by mutated hematopoietic stem cells, characterized by an increased risk of thrombosis and progression to leukemia. Patients with MPN exhibit elevated levels of inflammatory factors, which function as promoters of disease progression and transformation into acute leukemia. Fufang Huangbo formula (FHF) is a classic traditional Chinese herbal medicine widely used in the treatment of inflammation-related diseases, where it has shown considerable therapeutic efficacy. However, its potential effects on MPNs remain unclear. In this study, we demonstrate for the first time across multiple animal models that FHF significantly alleviates MPN progression, including EPO-induced polycythemia vera (PV)-like, JAK2 V617F -driven PV, and MPL W515L -driven essential thrombocythemia (ET) models. FHF effectively reduced erythrocyte aggregation-induced thrombosis in PV and reversed myelofibrosis in ET. To explore the therapeutic effects, active components, and mechanisms of FHF in MPNs, we performed network pharmacology and RNA-seq analyses, with subsequent experimental validation. The results indicate that the therapeutic benefits of FHF are closely associated with cellular senescence and inflammatory responses. Validation experiments showed that FHF induces cellular senescence via activation of the p53/p21 pathway and suppresses inflammation by inhibiting the STAT3 and NF-κB signaling pathways. Our study provides scientific evidence supporting the use of FHF in the treatment of MPNs. • The treatment of FHF effectively alleviated the disease burden and progression of MPNs mouse models caused by EPO high -induced PV-like disease, JAK2 V617F -driven PV, and MPL W515L -driven ET. • FHF inhibits the proliferation of MPN cells by inducing cellular senescence through activation of the p53/p21 signaling pathway. • FHF improves the progression of MPNs by inhibiting the STAT3 and NF-κB signaling pathways.
Liu et al. (2026) studied this question.