Relationship Between Iron and Erythropoiesis

In recent years there has been important advancement in our knowledge of iron metabolism regulation that also has implications for understanding the physiopathology of some human disorders like beta-thalassemia and other iron overload diseases. In fact, progressive iron overload is the most salient and ultimately fatal complication of beta-thalassemia. Iron deposition occurs in visceral organs (mainly in the heart, liver and endocrine glands), causing tissue damage and ultimately organ dysfunction and failure. Both transfusional iron overload and excess gastrointestinal absorption are contributory. Paradoxically, excess gastrointestinal iron absorption persists despite massive increases in total body iron load. However, little is known about the relationship among ineffective erythropoiesis, the role of iron-regulatory genes, and tissue iron distribution in beta-thalassemia. The focus of this chapter is an update about iron homeostasis and erythroid differentiation with a particular attention to the molecular mechanisms of iron homeostasis deregulation in thalassemia and to the GDF15-BMP-Hepcidin-Ferroportin regulatory pathway in order to understand the contribution to iron overload. The chapter describes evidences for these relationships and discusses how recent discoveries on iron metabolism and erythropoiesis could lead to new therapeutic strategies and better clinical care of these diseases, thereby yielding a much better quality of life for the patients.