JAK2V617F-mutated hemogenic endothelium as cell of origin in PMF

Current understanding

Preclinical evidence suggests that JAK2V617F-mutated mature endothelial cells in primary myelofibrosis can behave as embryonic-like hemogenic endothelium, displaying multilineage clonogenic potential and potentially constituting the malignant stem cell pool. This reframes MPN ontogenesis by proposing the vascular endothelium — not solely the bone marrow HSC compartment — as the cell of origin for clonal hematopoiesis in PMF, repositioning endothelial-to-hematopoietic transition as a candidate disease-initiating event.

Evidence log

• 2026-03-20 — Association between JAK2 Mutations and Thoracic Aortic Aneurysms in Myeloproliferative Neoplasms: cross-connection with jak2-thoracic-aortic-aneurysm-vasculopathy: 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)
• 2026-05-26 — JAK2V617F Mutated Endothelium Has a Stem Cell Potential in Primary Myelofibrosis: a New Disease Ontogenesis for Chronic Myeloproliferative Disorders: cross-connection with clonal-hematopoiesis: Reassigns the cell of origin of MPN clonal hematopoiesis from the HSC compartment to JAK2V617F-mutated hemogenic endothelium. (novelty: 5)

Open questions

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