Model of erythroid amplification and selective advantage for JAK2 617V>F–positive ET and PV patients. The left diagram shows a model of erythropoiesis from the hematopoietic stem cells (HSC) to the mature erythroblasts (GPA⁺) via CD34⁺CD38⁻ immature progenitor cells, CD34⁺CD38⁺ and BFU-E committed progenitor cells. In comparison with normal erythropoiesis (white diagram), a moderate late amplification driven by a low percentage of heterozygous mutant cells leads to mild erythrocytosis in ET (gray diagram), whereas major amplification of the terminal erythroid differentiation due to the presence of homozygous subclones is observed in homozygous PV (black diagram). Most BFU-E from PV patients with a heterozygous profile (hatched diagram) are mutated. Thus, selective amplification may occur upstream from this stage of differentiation. Further terminal erythroid amplification of the predominant mutated clone results in severe erythrocytosis. The right diagram shows the selective pressure due to the decrease in the level of serum Epo caused by erythrocytosis.