Regular Article RED CELLS, IRON, AND ERYTHROPOIESIS

develop hemolytic anemia with acanthocyte red blood cells and display compensatory extramedullary erythropoiesis. • Hyperactive Lyn notably alters Epo receptor signaling, particularly an Akt-FoxO3 pathway, enhancing viability and delaying differentiation. Lyn is involved in erythropoietin (Epo)-receptor signaling and erythroid homeostasis. Downstream pathways influenced following Lyn activation and their significance to erythropoiesis remain unclear. To address this, we assessed a gain-of-function Lyn mutation (Lynup/up) on erythropoiesis and Epo receptor signaling. Adult Lynup/upmice were anemic, with dysmorphic red cells (spherocyte-like, acanthocytes) in their circulation, indicative of hemolytic anemia and resembling the human disorder chorea acanthocytosis