Biomarker analysis in polycythemia vera under interferon-alpha treatment: clonality, EEC, PRV-1, and JAK2 V617F

Three consecutive polycythemia vera (PV) patients were analyzed before and during pegylated-interferon (rIFN alpha) treatment for the following markers: (1) granulocyte and CD34(+) stop cell clonality, (2) Jak2V617F expression, (3) PRV-1 mRNA overexpression, and (4) Epo-independent colony (EEC) growth. Before rIFN alpha therapy, all patients displayed clonal hematopoiesis, 100% Jak2V617F expression as well as PRV-1 overexpression, and EEC growth. After rIFN alpha treatment, all three patients demonstrated polyclonal hematopoiesis. Nonetheless, Jak2V617F expression, PRV-1 overexpression, and EEC-growth remained detectable, albeit at lower levels. We conclude that reemergence of polyclonal hematopoiesis after rIFN alpha treatment may be achieved in a substantial proportion of patients. However, this does not constitute elimination of the PV clone. These data demonstrate the usefulness of novel markers in monitoring minimal residual disease and caution against discontinuation of rIFN alpha treatment after hematologic remission. Long-term follow-up of large patient cohorts is required to determine whether rIFN alpha treatment can cause complete molecular remissions in PV.