IRON METABOLISM IN HEMATOPOIESIS: IMPLICATIONS FOR ANEMIA, BONE MARROW FAILURE, AND THERAPEUTIC TARGETING

Abstract

Iron is a vital micronutrient that is important in normal hematopoiesis especially erythropoiesis and hemoglobin production. Its macro and cellular homeostasis is highly coordinated with mechanisms that include intestinal absorption, recycling with the help of macrophages and hormonal control; hepcidin being the major hormone to maintain homeostasis. Iron imbalance, both deficiency and overload, have a dramatic negative effect on hematopoietic processes and has been implicated in an extensive repertoire of hematologic conditions, including iron-deficiency anemia, anemia of inflammation and iron overload syndromes. New developments have emphasized the expanded role of iron beyond the synthesis of hemoglobin, such as iron being involved in the maintenance of hematopoietic stem cell and cellular proliferation, mitochondrial activity, and redox regulation. The interaction of iron metabolism and hematopoiesis is conditioned by multimodular molecular mechanisms that guarantee the sufficient supply of iron and avoid toxicity. This review emphasizes the existing knowledge regarding the molecular pathways through which iron homeostasis is connected with hematopoietic control with emphasis on the iron transport, hepcidin regulation, and erythroid differentiation. Moreover, it addresses the pathological implications of iron metabolism dysregulation and dwells upon the new therapeutic approaches aimed at addressing the iron-mediated pathways in hematologic disorders.