Exogenous iron increases hemoglobin in beta-thalassemic mice.
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.


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.
Ginzburg
Yelena Z
YZ
Erythropoiesis Laboratory, New York Blood Center, New York, NY 10065, USA. yginzburg@nybloodcenter.org
Rybicki
Anne C
AC
Suzuka
Sandra M
SM
Hall
Charles B
CB
Breuer
William
W
Cabantchik
Z Ioav
ZI
Bouhassira
Eric E
EE
Fabry
Mary E
ME
Nagel
Ronald L
RL
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis / Q000235:genetics; D001853:Bone Marrow / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D015672:Erythroid Precursor Cells / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects* / Q000235:genetics; D006397:Hematinics / Q000494:pharmacology*; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects* / Q000235:genetics; D006454:Hemoglobins / Q000096:biosynthesis* / Q000235:genetics; D064451:Hepcidins; D007501:Iron / Q000378:metabolism; D007505:Iron-Dextran Complex / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D017086:beta-Thalassemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; C579599:Hamp protein, mouse; D006397:Hematinics; D006454:Hemoglobins; D064451:Hepcidins; D007505:Iron-Dextran Complex; D007501:Iron