JAK2V617F 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 JAK2V617F 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 JAK2V617F mutation burden in the pathogenesis and natural history of PV, suitability of JAK2V617F VAF as a diagnostic and prognostic biomarker, and utility of JAK2V617F VAF reduction in PV treatment.