-Thalassemia: HiJAKing Ineffective Erythropoiesis and Iron Overload
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.