NFκB/IL-6/JAK2/STAT axis in myelofibrosis is a key vulnerability that is targetable and relevant to JAK2 inhibitor treatment resistance
Abstract
Myelofibrosis (MF) is a chronic myeloproliferative neoplasm (MPN) characterized by bone marrow (BM) fibrosis, splenomegaly, and ineffective erythropoiesis [ 1 ]. Its complex pathogenesis involves constitutional JAK/STAT hyperactivation, elevated cytokines, and hyperactive NFκB [ 2 ], though the precise interactions of these pathways are unclear. Current JAK2 inhibitors (JAKi) alleviate symptoms like splenomegaly and improve quality of life but lacks disease-modifying activity, and resistance is common, leading to disease progression [ 3 ]. One documented resistance mechanism involves a paradoxical JAK2 hyperphosphorylation upon treatment [ 4 ], which prevents dephosphorylation at the Tyr1007/1008 site [ 5 ]. However, the precise molecular mechanisms driving this process remain unknown.
Fields of Study & Subjects
Myeloproliferative Neoplasms: Diagnosis and Treatment
Cytokine Signaling Pathways and Interactions
Vasculitis and related conditions
Publication details
- Journal / source
- Blood Cancer Journal
- Publisher
- Springer Science and Business Media LLC
- Volume
- 16
- Issue
- 1
- Pages
- 13–13
- Publication date
- 12 January 2026
- Language
- EN