Exogenous iron increases hemoglobin in β-thalassemic mice

Yelena Z. Ginzburg, Anne C. Rybicki, Sandra M. Suzuka, Charles B. Hall, William Breuer, Z. Ioav Cabantchik, Eric E. Bouhassira, Mary E. Fabry, Ronald L. Nagel

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Objective: β-thalassemia results from β-globin gene mutations that lead to ineffective erythropoiesis, shortened red cell survival, and anemia. Patients with β-thalassemia develop iron overload, despite which, hepcidin levels are low. This suggests that hepcidin regulation in β-thalassemia is more sensitive to factors unrelated to iron state. Our preliminary data demonstrates that Hbbth1/th1 mice, a model of β-thalassemia intermedia, have lower bone marrow iron levels while levels in the liver and spleen are increased; the later account for the increased systemic iron burden in β-thalassemia intermedia. We hypothesized that exogenous iron would improve anemia in β-thalassemia intermedia despite systemic iron overload and further suppress hepcidin secondary to progressive expansion of erythroid precursors. Materials and Methods: We investigate parameters involved in red cell production, precursor apoptosis, parenchymal iron distribution, and hepcidin expression in iron treated Hbbth1/th1 mice. Results: Exogenous iron results in an expansion of erythroid precursors in the liver and spleen, leading to an increase in the number of red cells, reticulocytes, and hemoglobin production. A decrease in hepcidin expression is also observed. Conclusions: These findings demonstrate for the first time that iron results in expansion of extramedullary erythropoiesis, which improves anemia and suggests that expansion of extramedullary erythropoiesis itself results in hepcidin suppression in β-thalassemia intermedia.

Original languageEnglish (US)
Pages (from-to)172-183
Number of pages12
JournalExperimental Hematology
Issue number2
StatePublished - Feb 2009
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research


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