JAK2-driven vasculopathy and thoracic aortic aneurysm
Current understanding
A scoping review identifies an association between JAK2 mutations in MPN and thoracic aortic aneurysm (TAA), implicating JAK2-driven clonal hematopoiesis and/or mutant endothelium in large-vessel wall remodeling beyond the canonical thrombotic complications. Proposed mechanisms include JAK-STAT-mediated inflammatory cytokine signaling, mutant endothelial contribution to vascular wall integrity, and clonal myeloid infiltration of the aortic wall. Evidence tier is review-level synthesis; causal mechanism and prospective risk quantification remain to be established.
Evidence log
- 2025-11-20 — Splenic Artery Aneurysm Associated with Myelofibrosis Managed by Coil Embolization.: Case report of splenic artery aneurysm in JAK2 V617F secondary MF extends the JAK2-associated aneurysm phenotype beyond the thoracic aorta to splanchnic arteries, and shows ruxolitinib-mediated spleen volume reduction can normalize downstream hemodynamics sufficiently to enable endovascular repair. (novelty: 3)
- 2026-03-20 — Association between JAK2 Mutations and Thoracic Aortic Aneurysms in Myeloproliferative Neoplasms: cross-connection with jak2v617f-hemogenic-endothelium-cell-of-origin: JAK2V617F-mutant endothelium could provide a direct mechanistic substrate linking MPN clonal biology to aortic wall pathology, connecting the new TAA association to the endothelial cell-of-origin hypothesis. (novelty: 4)