Molecular and clinical features of the myeloproliferative neoplasm associated with JAK2 exon 12 mutations.

While about 95% of patients with polycythemia vera (PV) harbor the V617F mutation in JAK2 exon 14, several mutations in exon 12 have been described in the remaining patients. We conducted a European collaborative study to define the molecular and clinical features of patients harboring these mutations. Overall, 106 PV were recruited and 17 different mutations identified. Irrespective of the mutation, two thirds of patients had isolated erythrocytosis, while the remaining subjects had erythrocytosis plus leukocytosis and/or thrombocytosis. When compared to JAK2 (V617F)-positive PV patients, those with exon 12 mutations had significantly higher hemoglobin level and lower platelet and leukocyte counts at diagnosis, but similar incidences of thrombosis, myelofibrosis, leukemia and death. In a multivariable analysis, age over 60 years and prior thrombosis predicted thrombosis. These findings suggest that, despite the phenotypical difference, the outcome of JAK2 exon 12 mutations-positive PV is similar to that of JAK2 (V617F)-positive PV.