JAK2 V617F Mutation Testing in Polycythemia Vera: Use and Impact in a Single Academic Practice.

The observation that a gain-of-function mutation in JAK2 (JAK2 V617F) is present in more than 90% of cases of polycythemia vera (PV) has substantially revised the diagnostic approach to this disease. However, most studies of the utility of JAK2 V617 derive from large PV populations: the majority of hematologists have relatively few PV patients in their individual practices. In order to assess the effect of JAK2 V617F analysis in practices with a small PV population, the utilization and impact of this test in 5 individual clinics in a single academic practice were analyzed. Sixteen patients (15 male) carrying a diagnosis of PV were identified. Five patients were followed in a clinic at a University medical center staffed by a single attending hematologist; one was followed by that attending physician in a clinic at the affiliated VA hospital; and 10 were followed by Hematology/Oncology Fellows in three continuity clinics at the affiliated VA hospital. In these latter clinics, the Fellow is primary provider, but reviews management with an attending physician. Median age of the overall population was 67.5 yrs; patients in the Fellow clinics were significantly older than those in the Attending clinics (80 yrs vs. 63 yrs; p < 0.01). Duration of disease was longer in the Fellow clinic patients than the Attending patients (8.5 yrs vs. 1.4 yrs; p=0.05). Nine patients were tested for JAK2 V617F mutation. The majority (6/9) were tested near diagnosis (median duration of erythrocytosis was 0.7 yrs for patients tested and 10 yrs for patients not tested; p = 0.02). Two of the three established patients tested did not meet PV diagnostic criteria fully. Five of the 7 not tested met WHO criteria for PV. Of the 9 patients tested, 7 had a mutation detected (5 newly diagnosed, 2 > 1 yr duration of disease). Results of mutation testing changed the diagnosis in two cases (one where it was detected and one where it was not detected). In addition, one newly diagnosed patient who met WHO criteria did not have JAK2 V617F detected and was felt to have true “JAK2 V617F-negative” PV. JAK2 exon 12 studies were not performed.

Conclusions: The use and impact of JAK2 V617F mutation testing has been reviewed in a PV population similar to what an individual or small group practice might follow. JAK2 V617F mutation testing was primarily used in the early evaluation of suspected PV, or in continuing patients whose diagnosis was not fully established. Mutation testing was infrequently used in continuing patients where the physician considered the diagnosis clearly established or where a change in diagnosis would not alter management. Negative results of mutation testing altered diagnosis if they were consistent with the patient’s clinical picture.