In contrast, the fact that MK hyperplasia and fibrosis were only slightly modified by Fedratinib in our TPOHIGH models or by other JAK2 inhibitors in JAK2V617F late-phase disease models 43 suggests that the development of advanced stage myelofibrosis and associated pathological megakaryopoiesis become progressively JAK2-independent in MPN and refractory to JAK2 inhibitors. This evidence concerns the gene JAK2 and myeloproliferative neoplasm.