JAK2^V617F Allele Burden in Polycythemia Vera: Burden of Proof

Polycythemia vera (PV) is a hematopoietic stem cell (HSC) neoplasm defined by activating somatic mutations in the JAK2 gene and characterized clinically by overproduction of red blood cells, platelets, and neutrophils; significant burden of disease-specific symptoms; high rates of vascular events; and evolution to a myelofibrosis phase or acute leukemia. The JAK2^V617F variant allele frequency (VAF) is a key determinant of outcomes in PV, including thrombosis and myelofibrotic progression. Herein we critically review the dynamic role of JAK2^V617F mutation burden in the pathogenesis and natural history of PV, suitability of JAK2^V617F VAF as a diagnostic and prognostic biomarker, and utility of JAK2^V617F VAF reduction in PV treatment.