Model to explain the relationship of essential thrombocythemia, polycythemia vera and primary myelofibrosis. Whereas a phenotypic overlap exists between JAK2 V617F–positive polycythemia and thrombocythemia, JAK2 V617F–negative disease is both biologically distinct and heterogeneous, including 10% of patients with MPL mutations and 90% in whom the molecular cause is currently unknown. Accelerated phase disease may follow JAK2 V617F–positive or –negative chronic phase and is clinically variable, including bone marrow fibrosis, increasing or falling white cell count or splenomegaly. A minority of patients undergo disease evolution to acute myeloid leukemia. In this model, patients currently labeled as having primary myelofibrosis may in fact represent those presenting in accelerated phase of a pre-existing myeloproliferative neoplasm (MPN).
 Hb indicates hemoglobin; Plt, platelet count.