Figure 1: In normal erythropoiesis, physiological levels of EPO induce the phosphorylation of Jak2 in normal erythroid progenitors and sustain the differentiation to mature RBC (top of the figure). In β-thalassemia, the high levels of EPO induce an uncontrolled proliferation of erythroid precursors, with a higher number of cells associated with the phosphorylated form of Jak2. In β-thalassemia intermedia, where a certain amount of β-globin is still synthesized, there is a high production of reticulocytes that eventually mature in RBC. In β-thalassemia major, where there is a complete lack of β-globin, the orythroid progenitors continue to proliferate and fail to mature into reticulocytes and RBC or undergo apoptosis.