Quantitative, qualitative, and clonal burden in PV. (A) JAK2^V617F increases cell quantity by transmitting an excessive growth signal that induces a blood stem cell with the mutation to over produce red blood cells, white blood cells, and platelets. (B) JAK2^V617F excessive signaling in cells turns on ROS and HIF, resulting in activation of pathways within the HSC cell, the bone marrow niche, and beyond. (C) JAK2^V617F can be present in a single cell as a single copy (heterozygote, blue circle) or as a double copy (homozygote, red circle). Measured JAK2^V617F VAF in PV may range from 1% to 100%, depending on relative quantities of the various JAK2^V617F genotypes. HIF, hypoxia-inducible factor; ROS, reactive oxygen species.