title: Anemia, ineffective erythropoiesis, and hepcidin: interacting factors in abnormal iron metabolism leading to iron overload in β-thalassemia.
abstract: β-Thalassemia is a genetic disorder caused by mutations in the β-globin gene and characterized by chronic anemia caused by ineffective erythropoiesis, and accompanied by a variety of serious secondary complications such as extramedullary hematopoiesis, splenomegaly, and iron overload. In the past few years, numerous studies have shown that such secondary disease conditions have a genetic basis caused by the abnormal expression of genes with a role in controlling erythropoiesis and iron metabolism. In this article, the most recent discoveries related to the mechanism(s) responsible for anemia/ineffective erythropoiesis and iron overload are discussed in detail. Particular attention is paid to the pathway(s) controlling the expression of hepcidin, which is the main regulator of iron metabolism, and the Epo/EpoR/Jak2/Stat5 signaling pathway, which regulates erythropoiesis. Better understanding of how these pathways function and are altered in β-thalassemia has revealed several possibilities for development of new therapeutic approaches to treat of the complications of this disease.
authors.affiliation: Hematology-Oncology, Department of Pediatrics, Weill Cornell Medical College, 515 East 71st Street, New York, NY 10021, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Gardenghi
authors.forename: Robert W
authors.initials: RW
authors.lastname: Grady
authors.forename: Stefano
authors.initials: S
authors.lastname: Rivella
mesh_terms: D000740:Anemia / Q000378:metabolism*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D004920:Erythropoiesis; D004921:Erythropoietin / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism; D019190:Iron Overload; D017467:Receptors, Erythropoietin / Q000378:metabolism; D017086:beta-Thalassemia / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D007501:Iron