Exogenous iron increases hemoglobin in beta-thalassemic mice.

Abstract:

OBJECTIVE:Beta-thalassemia results from beta-globin gene mutations that lead to ineffective erythropoiesis, shortened red cell survival, and anemia. Patients with beta-thalassemia develop iron overload, despite which, hepcidin levels are low. This suggests that hepcidin regulation in beta-thalassemia is more sensitive to factors unrelated to iron state. Our preliminary data demonstrates that Hbb(th1/th1) mice, a model of beta-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 beta-thalassemia intermedia. We hypothesized that exogenous iron would improve anemia in beta-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 Hbb(th1/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 beta-thalassemia intermedia.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Ginzburg YZ,Rybicki AC,Suzuka SM,Hall CB,Breuer W,Cabantchik ZI,Bouhassira EE,Fabry ME,Nagel RL

doi

10.1016/j.exphem.2008.10.004

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

172-83

issue

2

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(08)00476-1

journal_volume

37

pub_type

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