期刊
BLOOD
卷 128, 期 2, 页码 265-276出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2015-10-676742
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资金
- Merganser Biotech
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Heart, Lung, and Blood Institute of the National Institutes of Health [DK095201, R01 DK090554, R01 DK107309, R01 DK107670, R01 DK095112, K08 HL105682]
- Cooley's Anemia Foundation
- Child Reach Foundation
In beta-thalassemia and polycythemia vera (PV), disordered erythropoiesis triggers severe pathophysiological manifestations. beta-Thalassemia is characterized by ineffective erythropoiesis, reduced production of erythrocytes, anemia, and iron overload and PV by erythrocytosis and thrombosis. Minihepcidins are hepcidin agonists that have been previously shown to prevent iron overload in murine models of hemochromatosis and induce iron-restricted erythropoiesis at higher doses. Here, we show that in young Hbb(th3/+) mice, which serve as a model of untransfused beta-thalassemia, minihepcidin ameliorates ineffective erythropoiesis, anemia, and iron overload. In older mice with untransfused beta-thalassemia, minihepcidin improves erythropoiesis and does not alter the beneficial effect of the iron chelator deferiprone on iron overload. In PV mice that express the orthologous JAK2 mutation causing human PV, administration of minihepcidin significantly reduces splenomegaly and normalizes hematocrit levels. These studies indicate that drug-like minihepcidins have a potential as future therapeutics for untransfused beta-thalassemia and PV.
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