title: Altered erythropoiesis and iron metabolism in carriers of thalassemia.
abstract: The thalassemia syndromes (α- and β-thalassemia) are the most common and frequent disorders associated with ineffective erythropoiesis. Imbalance of α- or β-globin chain production results in impaired red blood cell synthesis, anemia, and more erythroid progenitors in the blood stream. While patients affected by these disorders show definitive altered parameters related to erythropoiesis, the relationship between the degree of anemia, altered erythropoiesis, and dysfunctional iron metabolism has not been investigated in both α-thalassemia carriers (ATC) and β-thalassemia carriers (BTC). Here, we demonstrate that ATC have a significantly reduced hepcidin and increased soluble transferrin receptor levels but relatively normal hematological findings. In contrast, BTC have several hematological parameters significantly different from controls, including increased soluble transferrin receptor and erythropoietin levels. These changes in both groups suggest an altered balance between erythropoiesis and iron metabolism. The index sTfR/log ferritin and (hepcidin/ferritin)/sTfR are, respectively, increased and reduced relative to controls, proportional to the severity of each thalassemia group. In conclusion, we showed in this study, for the first time in the literature, that thalassemia carriers have altered iron metabolism and erythropoiesis.
authors.affiliation: Laboratório de Hematologia Clínica, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.|The Strauss Thalassemia Laboratory, Pediatric Hematology-Oncology, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Guimarães
authors.affiliation: Laboratório de Hematologia Clínica, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Juçara G
authors.initials: JG
authors.lastname: Cominal
authors.affiliation: Centro Regional de Hemoterapia de Ribeirão Preto, Departamento de Medicina Interna, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Silva-Pinto
authors.affiliation: Intrinsic LifeSciences, LLC, La Jolla, CA, USA.
authors.forename: Gordana
authors.initials: G
authors.lastname: Olbina
authors.affiliation: New York Blood Center, New York, NY, USA.
authors.forename: Yelena Z
authors.initials: YZ
authors.lastname: Ginzburg
authors.affiliation: New York Blood Center, New York, NY, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Nandi
authors.affiliation: Intrinsic LifeSciences, LLC, La Jolla, CA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Westerman
authors.affiliation: The Strauss Thalassemia Laboratory, Pediatric Hematology-Oncology, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rivella
authors.affiliation: Laboratório de Hematologia Clínica, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: de Souza
mesh_terms: D001782:Blood Donors; D004909:Erythrocyte Indices; D004920:Erythropoiesis / Q000235:genetics*; D005293:Ferritins / Q000097:blood / Q000378:metabolism; D064451:Hepcidins / Q000097:blood / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism*; D009154:Mutation; D013789:Thalassemia / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D055542:alpha-Globins / Q000235:genetics; D055544:beta-Globins / Q000235:genetics
chemical_list: D064451:Hepcidins; D055542:alpha-Globins; D055544:beta-Globins; D005293:Ferritins; D007501:Iron
keywords: GDF15; erythropoiesis; erythropoietin; ferritin; hepcidin; iron metabolism; soluble transferrin receptor; thalassemia