The V617F JAK2 Mutation Is Very Uncommon in Idiopathic Erythrocytosis.

The V617F JAK2 mutation is highly frequent in Polycythemia Vera (PV) patients. Indeed, we and others found the mutation in 70 to 90% of PV patients. However one of the most difficult differential diagnoses of PV is the idiopathic erythrocytosis (IE), as this diagnosis is based on negative criteria and exclusion of PV. However the differential diagnosis is of the utmost importance because IE is not considered as a clonal disease and should not transform to PV. Our centre is specialized in the diagnosis of myeloproliferative diseases, thus we have reviewed 22 cases with pure idiopathic erythrocytosis in the aim of defining the impact of V617F JAK2 mutation in this pathology. Median age of the patients was 46 (range: 29 to 67). Patients were diagnosed on the basis of an elevation of the hematocrit and a raised red cell mass without any identifiable cause of secondary erythrocytosis. PV diagnosis has been carefully excluded according to revised Pearson’s criteria. Median excess of red cell mass was +35% (range: +25% to +104%). Median hematocrit was 54% (range: 49% to 56%), median WBC (x10⁹/L) was 6180 (range: 3500 – 8300) and median platelet count (x10⁹/L) was 240 (range: 174 – 358). Serum Epo level was under or within the normal range in all patients except one case in whom an unexplained elevated level (x2 the upper normal limit) was found. Finally no splenomegaly was observed in these 22 patients. Because of the importance of a correct diagnosis distinguishing between PV and IE it was very important to test whether the JAK2 mutation could allow a correct classification. We have analysed DNA isolated from peripheral blood granulocytes. V617F JAK2 mutation was detected using a quantitative PCR and Taqman probes with a sensitivity of 2–4%. All of the 22 patients with IE were tested negative. This result confirms

1. that IE is a distinct entity from PV, and also

2. confirms the potential for the V617F JAK2 mutation detection to help in the differential diagnosis of erythrocytosis. Indeed, the presence of a JAK2 mutation in the context of erythrocytosis with increased red cell mass is highly specific of PV.