title: Minihepcidin peptides as disease modifiers in mice affected by β-thalassemia and polycythemia vera.
abstract: In β-thalassemia and polycythemia vera (PV), disordered erythropoiesis triggers severe pathophysiological manifestations. β-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 β-thalassemia, minihepcidin ameliorates ineffective erythropoiesis, anemia, and iron overload. In older mice with untransfused β-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 β-thalassemia and PV.
authors.affiliation: Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Division of Hematology-Oncology, Department of Pediatrics, Weill Cornell Medical College, New York, NY;
authors.forename: Carla
authors.identifier: 0000-0001-8458-1786
authors.initials: C
authors.lastname: Casu
authors.affiliation: Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Division of Hematology-Oncology, Department of Pediatrics, Weill Cornell Medical College, New York, NY;
authors.forename: Paraskevi Rea
authors.initials: PR
authors.lastname: Oikonomidou
authors.affiliation: Erythropoiesis Laboratory, and.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Laboratory Data Analytic Services, New York Blood Center, New York, NY;
authors.forename: Vijay
authors.initials: V
authors.lastname: Nandi
authors.affiliation: Erythropoiesis Laboratory, and.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Ginzburg
authors.affiliation: Department of Pediatrics, and.
authors.forename: Princy
authors.initials: P
authors.lastname: Prasad
authors.affiliation: Department of Pediatrics, and Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO;
authors.forename: Robert E
authors.initials: RE
authors.lastname: Fleming
authors.affiliation: Department of Molecular and Integrative Physiology, and Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI;
authors.forename: Yatrik M
authors.initials: YM
authors.lastname: Shah
authors.affiliation: Department of Medicine, and.
authors.forename: Erika V
authors.initials: EV
authors.lastname: Valore
authors.affiliation: Department of Medicine, and.
authors.forename: Elizabeta
authors.initials: E
authors.lastname: Nemeth
authors.affiliation: Department of Medicine, and Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA;
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
authors.affiliation: Merganser Biotech Inc., King of Prussia, PA;
authors.forename: Brian
authors.initials: B
authors.lastname: MacDonald
authors.affiliation: Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Division of Hematology-Oncology, Department of Pediatrics, Weill Cornell Medical College, New York, NY; Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY; and Cell and Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, PA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rivella
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D004920:Erythropoiesis; D064451:Hepcidins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D020125:Mutation, Missense; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011087:Polycythemia Vera / Q000235:genetics / Q000378:metabolism*; D017086:beta-Thalassemia / Q000235:genetics / Q000378:metabolism*
chemical_list: D064451:Hepcidins; D010455:Peptides; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2