Iron metabolism and ineffective erythropoiesis in β-thalassemia mouse models

Annals of the New York Academy of Sciences

Volumn 1202, Issue , 2010, Pages 24-30

  Ramos, Pedro ^a,b   Melchiori, Luca ^a   Gardenghi, Sara ^a   Van Roijen, Nico ^c   Grady, Robert W ^a   Ginzburg, Yelena ^d   Rivella, Stefano ^a  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

^b UNIVERSITY OF PORTO   (Portugal)

^c VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^d NEW YORK BLOOD CENTER   (United States)

Author keywords

hepcidin; ineffective erythropoiesis; iron overload; Jak2; transferrin; thalassemia

Indexed keywords

BETA GLOBIN; HEPCIDIN;

ANEMIA; BETA THALASSEMIA; BONE MARROW; CELL DEATH; CELL PROLIFERATION; CONFERENCE PAPER; ERYTHROCYTE; ERYTHROID PRECURSOR CELL; ERYTHROPOIESIS; EXTRAMEDULLARY HEMATOPOIESIS; HEMOLYSIS; HEPATOSPLENOMEGALY; HUMAN; IRON ABSORPTION; IRON METABOLISM; IRON OVERLOAD; NONHUMAN; PATIENT CARE; SPLENECTOMY; SPLENOMEGALY;

EID: 77955870192     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1111/j.1749-6632.2010.05596.x     Document Type: Conference Paper

References (37)

1. Bannerman, R.M. et al. 1967. Thalassemia intermedia, with iron overload, cardiac failure, diabetes mellitus, hypopituitarism and porphyrinuria. Am. J. Med. 42: 476-486.
2. Finch, C.A. & P. Sturgeon. 1957. Erythrokinetics in Cooley's anemia. Blood 12: 64-73.
3. Finch, C.A. et al. 1970. Ferrokinetics in man. Med. (Baltimore) 49: 17-53.
4. Yuan, J. et al. 1993. Accelerated programmed cell death (apoptosis) in erythroid precursors of patients with severe beta-thalassemia (Cooley's anemia). Blood 82: 374-377.
5. Mathias, L.A. et al. 2000. Ineffective erythropoiesis in beta-thalassemia major is due to apoptosis at the polychromatophilic normoblast stage. Exp. Hematol. 28: 1343-1353.
6. Ponka,P. 1997.Tissue-specific regulation of iron metabolism and heme synthesis: distinct control mechanisms in erythroid cells. Blood 89: 1-25.
7. Chen, J.J. 2007. Regulation of protein synthesis by the hemeregulated eIF2alpha kinase: relevance to anemias. Blood 109: 2693-2699.
8. Shinar, E. et al. 1987. Erythrocyte membrane skeleton abnormalities in severe beta-thalassemia. Blood 70: 158-164.
9. Cappellini, M.D. et al. 1999. Metabolic indicators of oxidative stress correlate with haemichrome attachment to membrane, band 3 aggregation and erythrophagocytosis in betathalassaemia intermedia. Br. J. Haematol. 104: 504-512.
10. Kuypers, F.A. et al. 1998.Membrane phospholipid asymmetry in human thalassemia. Blood 91: 3044-3051.
11. Kong, Y. et al. 2004. Loss of alpha-hemoglobin-stabilizing protein impairs erythropoiesis and exacerbates betathalassemia. J. Clin. Invest. 114: 1457-1466.
12. Libani, I.V. et al. 2008. Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in betathalassemia. Blood 112: 875-885.
13. Origa, R. et al. 2007. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica 92: 583-588.
14. Gardenghi, S. et al. 2007. Ineffective erythropoiesis in betathalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. Blood 109: 5027-5035.
15. Melchiori, L. et al. 2009. Use of Jak2 Inhibitors to limit ineffective erythropoiesis and iron absorption in Mice affected by-thalassemia and other disorders of red cell production. Blood 114: 2020.
16. Rivella, S. 2009. Ineffective erythropoiesis and thalassemias. Curr. Opin. Hematol. 16: 187-194.
17. Chen,K. et al. 2009.Resolving the distinct stages in erythroid differentiation based on dynamic changes in membrane protein expression during erythropoiesis. Proc. Natl. Acad. Sci. USA 106: 17413-17418.
18. Cappellini, M.D. et al. 2000. Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia. Br. J. Haematol. 111: 467-473.
19. Ataga, K.I., M.D. Cappellini & E.A. Rachmilewitz. 2007. Beta-thalassaemia and sickle cell anaemia as paradigms of hypercoagulability. Br. J. Haematol. 139: 3-13.
20. Taher, A.T. et al. 2008. Thalassemia and hypercoagulability. Blood Rev. 22: 283-292.
21. Eldor, A. & E.A. Rachmilewitz. 2002. The hypercoagulable state in thalassemia. Blood 99: 36-43.
22. Rechavi, G. & S. Rivella. 2008. Regulation of iron absorption in hemoglobinopathies. Curr. Mol. Med. 8: 646-662.
23. Rivella, S. & E. Rachmilewitz. 2009. Future alternative therapies for-thalassemia. Expert Rev. Hematol. 2: 685-697.
24. Jenkins, Z.A. et al. 2007. Iron homeostasis during transfusional iron overload in beta-thalassemia and sickle cell disease: changes in iron regulatory protein, hepcidin, and ferritin expression. Pediatr. Hematol. Oncol. 24: 237-243.
25. Kattamis, A. et al. 2006. The effects of erythropoetic activity and iron burden on hepcidin expression in patients with thalassemia major. Haematologica 91: 809-812.
26. Pak, M. et al. 2006. Suppression of hepcidin during anemia requires erythropoietic activity. Blood 108: 3730-3735.
27. Weizer-Stern,O. et al. 2006.Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell-line HepG2 induced by thalassaemic sera.Br. J. Haematol. 135: 129-138.
28. Tanno, T. et al. 2007. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat. Med. 13: 1096-1101.
29. Tanno, T. et al. 2009. Identification of TWSG1 as a second novel erythroid regulator of hepcidin expression in murine and human cells. Blood 114: 181-186.
30. Skow, L.C. et al. 1983. Amouse model for beta-thalassemia. Cell 34: 1043-1052.
31. Li, H. et al. 2010. Transferrin therapy ameliorates disease in beta-thalassemic mice. Nat. Med. 16: 177-182.
32. Chasis, J.A. & N. Mohandas. 2008. Erythroblastic islands: niches for erythropoiesis. Blood 112: 470-478.
33. Theurl, M. et al. 2008. Kupffer cells modulate iron homeostasis in mice via regulation of hepcidin expression. J.Mol. Med. 86: 825-835.
34. Makui, H. et al. 2005. Contribution of Hfe expression in macrophages to the regulation of hepatic hepcidin levels and iron loading. Blood 106: 2189-2195.
35. Van Rooijen,N. & A. Sanders. 1994. Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J. Immunol. Methods 174: 83-93.
36. Giuliani, A.L. et al. 2001. Changes in murine bone marrow macrophages and erythroid burst-forming cells following the intravenous injection of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP). Eur. J. Haematol. 66: 221-229.
37. Ramos, P. et al. 2009. Macrophage depletion leads to modification of thalassemic phenotype. Blood 114: 2023.