The observation that major inflammatory cytokines are produced independently of MPN-associated mutations and the demonstration that JAK2-V617F can be a late event in MPN development are consistent with the hypothesis that chronic stimulation of myelopoiesis (via inflammation) may precede the acquisition of mutation in the JAK2 (MPL and CALR)? The gene discussed is MPL; the disease is myeloproliferative neoplasm.