Iron toxicity and its possible association with treatment of Cancer: Lessons from hemoglobinopathies and rare, transfusion-dependent anemias

Free Radical Biology and Medicine

Volumn 79, Issue , 2015, Pages 343-351

  Puliyel, Mammen ^a   Mainous, Arch G ^b   Berdoukas, Vasilios ^a   Coates, Thomas D ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b UNIVERSITY OF FLORIDA   (United States)

Author keywords

Cancer; Epidemiology; Hemoglobinopathy; Iron toxicity; Outcomes; Transferrin saturation

Indexed keywords

FERRITIN; FERROPORTIN; HEME; HEMOGLOBIN A1C; HEMOSIDERIN; HEPCIDIN; IRON; TRANSFERRIN; VERY LOW DENSITY LIPOPROTEIN;

ANEMIA; APLASTIC ANEMIA; BLOOD TRANSFUSION; BONE MARROW TRANSPLANTATION; CANCER RISK; CANCER SURVIVOR; CANCER THERAPY; CONGENITAL DYSERYTHROPOIETIC ANEMIA; ERYTHROPOIESIS; FERRITIN BLOOD LEVEL; GLUCOSE TOLERANCE; HEALTH HAZARD; HEMOCHROMATOSIS; HEMOGLOBINOPATHY; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; IRON ABSORPTION; IRON BINDING CAPACITY; IRON BLOOD LEVEL; IRON CHELATION; IRON INTAKE; IRON METABOLISM; IRON OVERLOAD; LIPID PEROXIDATION; MYELODYSPLASTIC SYNDROME; NON INSULIN DEPENDENT DIABETES MELLITUS; PANCREAS ISLET CELL; PHLEBOTOMY; PRIORITY JOURNAL; REVIEW; THALASSEMIA; TRANSFERRIN SATURATION; ADVERSE EFFECTS; COMPLICATION; HEMOGLOBINOPATHIES; NEOPLASMS;

ANEMIA; BLOOD TRANSFUSION; HEMOGLOBINOPATHIES; HUMANS; IRON; NEOPLASMS;

EID: 84923226137     PISSN: 08915849     EISSN: 18734596     Source Type: Journal    
DOI: 10.1016/j.freeradbiomed.2014.10.861     Document Type: Review

References (145)

1. S.V. Torti, and F.M. Torti Iron and cancer: more ore to be mined Nat Rev Cancer 13 2013 342 355
2. A. Fonseca-Nunes, P. Jakszyn, and A. Agudo Iron and Cancer Risk - A Systematic Review and Meta-analysis of the Epidemiological Evidence Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 23 2014 12 31
3. Y. Beguin, M. Aapro, H. Ludwig, L. Mizzen, and A. Osterborg Epidemiological and nonclinical studies investigating effects of iron in carcinogenesis-A critical review Critical reviews in oncology/hematology 89 2014 1 15
4. L.M. Bystrom, M.L. Guzman, and S. Rivella Iron and Reactive Oxygen Species: Friends or Foes of Cancer Cells? Antioxid Redox Signal 2013
5. E. Angelucci, P. Muretto, A. Nicolucci, D. Baronciani, B. Erer, J. Gaziev, M. Ripalti, P. Sodani, S. Tomassoni, G. Visani, and G. Lucarelli Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation Blood 100 2002 17 21
6. J. Kato, K. Miyanishi, M. Kobune, T. Nakamura, K. Takada, R. Takimoto, Y. Kawano, S. Takahashi, M. Takahashi, Y. Sato, T. Takayama, and Y. Niitsu Long-term phlebotomy with low-iron diet therapy lowers risk of development of hepatocellular carcinoma from chronic hepatitis C Journal of gastroenterology 42 2007 830 836
7. C. Borgna-Pignatti, M.C. Garani, G.L. Forni, M.D. Cappellini, E. Cassinerio, C. Fidone, V. Spadola, A. Maggio, G. Restivo Pantalone, A. Piga, F. Longo, M.R. Gamberini, P. Ricchi, S. Costantini, D. D'Ascola, P. Cianciulli, M.E. Lai, M.P. Carta, A. Ciancio, P. Cavalli, M.C. Putti, S. Barella, G. Amendola, S. Campisi, M. Capra, V. Caruso, G. Colletta, and S. Volpato Hepatocellular carcinoma in thalassaemia. An update of the Italian Registry Br J Haematol 2014
8. S.P. Fortmann, B.U. Burda, C.A. Senger, J.S. Lin, and E.P. Whitlock Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. Preventive Services Task Force Ann Intern Med 159 2013 824 834
9. N.S. Chandel, and D.A. Tuveson The Promise and Perils of Antioxidants for Cancer Patients New England Journal of Medicine 371 2014 177 178
10. V. Ladis, G. Chouliaras, V. Berdoukas, A. Chatziliami, C. Fragodimitri, F. Karabatsos, J. Youssef, A. Kattamis, and M. Karagiorga-Lagana Survival in a large cohort of Greek patients with transfusion-dependent beta thalassaemia and mortality ratios compared to the general population Eur J Haematol 86 2011 332 338
11. B. Modell, M. Khan, M. Darlison, M.A. Westwood, D. Ingram, and D.J. Pennell Improved survival of thalassaemia major in the UK and relation to T2∗ cardiovascular magnetic resonance J Cardiovasc.Magn Reson. 10 2008 42
12. T.T. Tan, and L.M. Coussens Humoral immunity, inflammation and cancer Curr Opin Immunol 19 2007 209 216
13. S. Demaria, E. Pikarsky, M. Karin, L.M. Coussens, Y.C. Chen, E.M. El-Omar, G. Trinchieri, S.M. Dubinett, J.T. Mao, E. Szabo, A. Krieg, G.J. Weiner, B.A. Fox, G. Coukos, E. Wang, R.T. Abraham, M. Carbone, and M.T. Lotze Cancer and inflammation: promise for biologic therapy Journal of immunotherapy 33 2010 335 351
14. T.D. Coates Physiology and pathophysiology of iron in hemoglobin-associated diseases Free Radic Biol Med 72 2014 23 40
15. K.S. Ruccione, K. Mudambi, R. Sposto, J. Fridey, S. Ghazarossian, and D.R. Freyer Association of projected transfusional iron burden with treatment intensity in childhood cancer survivors Pediatr Blood Cancer 59 2012 697 702
16. S.J. Bradley, I. Gosriwitana, S. Srichairatanakool, R.C. Hider, and J.B. Porter Non-transferrin-bound iron induced by myeloablative chemotherapy Br J Haematol 99 1997 337 343
17. L. Sahlstedt, L. von Bonsdorff, F. Ebeling, J. Parkkinen, E. Juvonen, and T. Ruutu Non-transferrin-bound iron in haematological patients during chemotherapy and conditioning for autologous stem cell transplantation Eur J Haematol 83 2009 455 459
18. L. Sahlstedt, F. Ebeling, L. von Bonsdorff, J. Parkkinen, and T. Ruutu Non-transferrin-bound iron during allogeneic stem cell transplantation Br J Haematol 113 2001 836 838
19. J.B. Porter Practical management of iron overload Br J Haematol 115 2001 239 252
20. V. Berdoukas, A. Nord, S. Carson, M. Puliyel, T. Hofstra, J. Wood, and T.D. Coates Tissue iron evaluation in chronically transfused children shows significant levels of iron loading at a very young age Am J Hematol 2013
21. R. Green, R. Charlton, H. Seftel, T. Bothwell, F. Mayet, B. Adams, C. Finch, and M. Layrisse Body iron excretion in man: a collaborative study Am J Med 45 1968 336 353
22. C. Beaumont, and F. Canonne-Hergaux [Erythrophagocytosis and recycling of heme iron in normal and pathological conditions; regulation by hepcidin] Transfus Clin Biol 12 2005 123 130
23. T. Ganz Systemic iron homeostasis Physiol Rev 93 2013 1721 1741
24. D.M. Frazer, and G.J. Anderson The regulation of iron transport BioFactors 40 2014 206 214
25. P. Ponka Rare causes of hereditary iron overload Semin Hematol 39 2002 249 262
26. E. Miyazaki, J. Kato, M. Kobune, K. Okumura, K. Sasaki, N. Shintani, P. Arosio, and Y. Niitsu Denatured H-ferritin subunit is a major constituent of haemosiderin in the liver of patients with iron overload Gut 50 2002 413 419
27. M.P. Weir, J.F. Gibson, and T.J. Peters Haemosiderin and tissue damage Cell biochemistry and function 2 1984 186 194
28. M. Kristiansen, J.H. Graversen, C. Jacobsen, O. Sonne, H.J. Hoffman, S.K. Law, and S.K. Moestrup Identification of the haemoglobin scavenger receptor Nature 409 2001 198 201
29. T. Ganz, and E. Nemeth Regulation of iron acquisition and iron distribution in mammals Biochim Biophys Acta 1763 2006 690 699
30. K.D. Poss, and S. Tonegawa Heme oxygenase 1 is required for mammalian iron reutilization Proc Natl Acad Sci U S A 94 1997 10919 10924
31. O. Loreal, I. Gosriwatana, D. Guyader, J. Porter, P. Brissot, and R.C. Hider Determination of non-transferrin-bound iron in genetic hemochromatosis using a new HPLC-based method J Hepatol 32 2000 727 733
32. A. Piga, F. Longo, L. Duca, S. Roggero, T. Vinciguerra, R. Calabrese, C. Hershko, and M.D. Cappellini High nontransferrin bound iron levels and heart disease in thalassemia major Am J Hematol 84 2009 29 33
33. Z.I. cabantchik, Y.S. Sohn, W. Breuer, and B.P. Esposito The molecular and cellular basis of iron toxicity in iron overlaod disorders. Diagnostic and therapeutic approaches Thalassemia Reports 3 2013 7 13
34. B.P. Esposito, W. Breuer, P. Sirankapracha, P. Pootrakul, C. Hershko, and Z.I. Cabantchik Labile plasma iron in iron overload: redox activity and susceptibility to chelation Blood 102 2003 2670 2677
35. R.C. Hider, and X.L. Kong Glutathione: a key component of the cytoplasmic labile iron pool Biometals 24 2011 1179 1187
36. T. Ganz, and E. Nemeth Iron metabolism: interactions with normal and disordered erythropoiesis Cold Spring Harbor perspectives in medicine 2 2012 a011668
37. A. Donovan, C.A. Lima, J.L. Pinkus, G.S. Pinkus, L.I. Zon, S. Robine, and N.C. Andrews The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis Cell Metab 1 2005 191 200
38. L. Cianetti, M. Gabbianelli, and N.M. Sposi Ferroportin and erythroid cells: an update Adv Hematol 2010 2010
39. B. Qiao, P. Sugianto, E. Fung, A. Del-Castillo-Rueda, M.J. Moran-Jimenez, T. Ganz, and E. Nemeth Hepcidin-induced endocytosis of ferroportin is dependent on ferroportin ubiquitination Cell Metab 15 2012 918 924
40. E. Nemeth Hepcidin biology and therapeutic applications Expert Rev Hematol 3 2010 153 155
41. Y.Q. Li, B. Bai, Q.Q. Zheng, H. Yan, and G.H. Zhuang Quantitative study of iron metabolism-related genes expression in rat Biomed Environ Sci 26 2013 808 819
42. N. Zhao, A.S. Zhang, and C.A. Enns Iron regulation by hepcidin J Clin Invest 123 2013 2337 2343
43. M.W. Hentze, M.U. Muckenthaler, B. Galy, and C. Camaschella Two to tango: regulation of Mammalian iron metabolism Cell 142 2010 24 38
44. S.R. Pasricha, D.M. Frazer, D.K. Bowden, and G.J. Anderson Transfusion suppresses erythropoiesis and increases hepcidin in adult patients with beta-thalassemia major: a longitudinal study Blood 122 2013 124 133
45. Z.M. Qian, Y.Z. Chang, G. Leung, J.R. Du, L. Zhu, Q. Wang, L. Niu, Y.J. Xu, L. Yang, K.P. Ho, and Y. Ke Expression of ferroportin1, hephaestin and ceruloplasmin in rat heart Biochim Biophys Acta 1772 2007 527 532
46. J.G. Parkes, E.W. Randell, N.F. Olivieri, and D.M. Templeton Modulation by iron loading and chelation of the uptake of non-transferrin-bound iron by human liver cells Biochim Biophys Acta 1243 1995 373 380
47. E.W. Randell, J.G. Parkes, N.F. Olivieri, and D.M. Templeton Uptake of non-transferrin-bound iron by both reductive and nonreductive processes is modulated by intracellular iron J Biol Chem 269 1994 16046 16053
48. G.Y. Oudit, H. Sun, M.G. Trivieri, S.E. Koch, F. Dawood, C. Ackerley, M. Yazdanpanah, G.J. Wilson, A. Schwartz, P.P. Liu, and P.H. Backx L-type Ca2+ channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy Nat Med 9 2003 1187 1194
49. S.K. Das, and G.Y. Oudit Voltage-gated Ca2+ channels as key mediators of iron-transport and iron-overload cardiomyopathy: L-type vs. T-type Ca+ channels Eur J Haematol 88 2012 476 477
50. R.G. Tsushima, A.D. Wickenden, R.A. Bouchard, G.Y. Oudit, P.P. Liu, and P.H. Backx Modulation of iron uptake in heart by L-type Ca2+ channel modifiers: possible implications in iron overload Circ Res 84 1999 1302 1309
51. P. Brissot, M. Ropert, C. Le Lan, and O. Loreal Non-transferrin bound iron: a key role in iron overload and iron toxicity Biochim Biophys Acta 1820 2012 403 410
52. P. Kirk, M. Roughton, J.B. Porter, J.M. Walker, M.A. Tanner, J. Patel, D. Wu, J. Taylor, M.A. Westwood, L.J. Anderson, and D.J. Pennell Cardiac T2∗ magnetic resonance for prediction of cardiac complications in thalassemia major Circulation 120 2009 1961 1968
53. L.J. Noetzli, A. Panigrahy, S.D. Mittelman, A. Hyderi, A. Dongelyan, T.D. Coates, and J.C. Wood Pituitary iron and volume predict hypogonadism in transfusional iron overload Am J Hematol 2011
54. L.J. Noetzli, S.D. Mittelman, R.M. Watanabe, T.D. Coates, and J.C. Wood Pancreatic iron and glucose dysregulation in thalassemia major Am J Hematol 2011
55. D.B. Kell, and E. Pretorius Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells Metallomics: integrated biometal science 6 2014 748 773
56. L.A. Cohen, L. Gutierrez, A. Weiss, Y. Leichtmann-Bardoogo, D.L. Zhang, D.R. Crooks, R. Sougrat, A. Morgenstern, B. Galy, M.W. Hentze, F.J. Lazaro, T.A. Rouault, and E.G. Meyron-Holtz Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway Blood 116 2010 1574 1584
57. D.A. Tsitsikas, R. Nzouakou, V. Ameen, B. Sirigireddy, and R.J. Amos Comparison of serial serum ferritin measurements and liver iron concentration assessed by MRI in adult transfused patients with sickle cell disease Eur J Haematol 92 2014 164 167
58. M. Puliyel, R. Sposto, V.A. Berdoukas, T.C. Hofstra, A. Nord, S. Carson, J. Wood, and T.D. Coates Ferritin trends do not predict changes in total body iron in patients with transfusional iron overload Am J Hematol 89 2014 391 394
59. G.M. Brittenham, A.R. Cohen, C.E. McLaren, M.B. Martin, P.M. Griffith, A.W. Nienhuis, N.S. Young, C.J. Allen, D.E. Farrell, and J.W. Harris Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major Am J Hematol 42 1993 81 85
60. E. Angelucci, G.M. Brittenham, C.E. McLaren, M. Ripalti, D. Baronciani, C. Giardini, M. Galimberti, P. Polchi, and G. Lucarelli Hepatic iron concentration and total body iron stores in thalassemia major N Engl J Med 343 2000 327 331
61. T.G. St Pierre, P.R. Clark, W. Chua-anusorn, A.J. Fleming, G.P. Jeffrey, J.K. Olynyk, P. Pootrakul, E. Robins, and R. Lindeman Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance Blood 105 2005 855 861
62. J.C. Wood, C. Enriquez, N. Ghugre, J.M. Tyzka, S. Carson, M.D. Nelson, and T.D. Coates MRI R2 and R2∗ mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients Blood 106 2005 1460 1465
63. L.J. Noetzli, J. Papudesi, T.D. Coates, and J.C. Wood Pancreatic iron loading predicts cardiac iron loading in thalassemia major Blood 114 2009 4021 4026
64. L.J. Anderson, S. Holden, B. Davis, E. Prescott, C.C. Charrier, N.H. Bunce, D.N. Firmin, B. Wonke, J. Porter, J.M. Walker, and D.J. Pennell Cardiovascular T2-star (T2∗) magnetic resonance for the early diagnosis of myocardial iron overload Eur Heart J 22 2001 2171 2179
65. J.C. Wood, C. Enriquez, N. Ghugre, M. Otto-Duessel, M. Aguilar, M.D. Nelson, R. Moats, and T.D. Coates Physiology and pathophysiology of iron cardiomyopathy in thalassemia Ann.N Y.Acad.Sci. 1054 2005 386 395
66. A. Pietrangelo Hereditary hemochromatosis - a new look at an old disease N Engl J Med 350 2004 2383 2397
67. D.H. Lee, D.Y. Liu, D.R. Jacobs Jr, H.R. Shin, K. Song, I.K. Lee, B. Kim, and R.C. Hider Common presence of non-transferrin-bound iron among patients with type 2 diabetes Diabetes Care 29 2006 1090 1095
68. C. Camaschella Iron and hepcidin: a story of recycling and balance Hematology Am Soc Hematol Educ Program 2013 2013 1 8
69. R.E. Fleming, and P. Ponka Iron Overload in Human Disease New England Journal of Medicine 366 2012 348 359
70. N.R. Ghugre, I. Gonzalez-Gomez, H. Shimada, T.D. Coates, and J.C. Wood Quantitative analysis and modelling of hepatic iron stores using stereology and spatial statistics J Microsc 238 2010 265 274
71. N.R. Ghugre, T.D. Coates, M.D. Nelson, and J.C. Wood Mechanisms of tissue-iron relaxivity: nuclear magnetic resonance studies of human liver biopsy specimens Magn Reson Med 54 2005 1185 1193
72. E.X. Wu, D. Kim, C.L. Tosti, H. Tang, J.H. Jensen, J.S. Cheung, L. Feng, W.Y. Au, S.Y. Ha, S.S. Sheth, T.R. Brown, and G.M. Brittenham Magnetic resonance assessment of iron overload by separate measurement of tissue ferritin and hemosiderin iron Ann N Y Acad Sci 1202 2010 115 122
73. T.S. Koskenkorva-Frank, G. Weiss, W.H. Koppenol, and S. Burckhardt The complex interplay of iron metabolism, reactive oxygen species, and reactive nitrogen species: insights into the potential of various iron therapies to induce oxidative and nitrosative stress Free Radic Biol Med 65 2013 1174 1194
74. S. Ghaffari Oxidative stress in the regulation of normal and neoplastic hematopoiesis Antioxid Redox Signal 10 2008 1923 1940
75. J. Glaspy Current status of use of erythropoietic agents in cancer patients Semin Thromb Hemost 40 2014 306 312
76. J.N. Barreto, K.B. McCullough, L.L. Ice, and J.A. Smith Antineoplastic agents and the associated myelosuppressive effects: a review Journal of pharmacy practice 27 2014 440 446
77. A. Reitman, K.S. Ruccione, T.D. Coates, and D.R. Freyer Significant cardiac iron overload in an 11-year-old child with acute lymphoblastic leukemia (ALL) after only one year of treatment Pediatr Blood Cancer 58 1055 2012 1618
78. J.C. Wood, R. Origa, A. Agus, G. Matta, T.D. Coates, and R. Galanello Onset of cardiac iron loading in pediatric patients with thalassemia major Haematologica 93 2008 917 920
79. J.M. Roob, G. Khoschsorur, A. Tiran, J.H. Horina, H. Holzer, and B.M. Winklhofer-Roob Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis J Am Soc Nephrol 11 2000 539 549
80. A.G. Mainous 3rd, R.U. Wright, M.M. Hulihan, W.O. Twal, C.E. McLaren, V.A. Diaz, G.D. McLaren, W.S. Argraves, and A.M. Grant Elevated transferrin saturation, health-related quality of life and telomere length Biometals 27 2014 135 141
81. C. Ellervik, H.U. Andersen, A. Tybjaerg-Hansen, M. Frandsen, H. Birgens, B.G. Nordestgaard, and T. Mandrup-Poulsen Total mortality by elevated transferrin saturation in patients with diabetes Diabetes Care 36 2013 2646 2654
82. C. Ellervik, A. Tybjaerg-Hansen, and B.G. Nordestgaard Total mortality by transferrin saturation levels: two general population studies and a metaanalysis Clin Chem 57 2011 459 466
83. K.S. Kim, H.G. Son, N.S. Hong, and D.H. Lee Associations of serum ferritin and transferrin % saturation with all-cause, cancer, and cardiovascular disease mortality: Third National Health and Nutrition Examination Survey follow-up study Journal of preventive medicine and public health=Yebang Uihakhoe chi 45 2012 196 203
84. A.G. Mainous 3rd, J.M. Gill, and P.J. Carek Elevated serum transferrin saturation and mortality Annals of family medicine 2 2004 133 138
85. A.G. Mainous 3rd, V.A. Diaz, M.E. Knoll, M.M. Hulihan, A.M. Grant, and R.U. Wright Transferrin saturation and hospital length of stay and mortality in Medicare beneficiaries J Am Geriatr Soc 61 2013 132 136
86. L.R. Zacharski, B.K. Chow, P.S. Howes, G. Shamayeva, J.A. Baron, R.L. Dalman, D.J. Malenka, C.K. Ozaki, and P.W. Lavori Decreased cancer risk after iron reduction in patients with peripheral arterial disease: results from a randomized trial Journal of the National Cancer Institute 100 2008 996 1002
87. K.V. Iron Kowdley hemochromatosis, and hepatocellular carcinoma Gastroenterology 127 2004 S79 86
88. A.G. Mainous 3rd, B.J. Wells, R.J. Koopman, C.J. Everett, and J.M. Gill Iron, lipids, and risk of cancer in the Framingham Offspring cohort Am J Epidemiol 161 2005 1115 1122
89. A.G. Mainous 3rd, J.M. Gill, and C.J. Everett Transferrin saturation, dietary iron intake, and risk of cancer Annals of family medicine 3 2005 131 137
90. C. Ellervik, T. Mandrup-Poulsen, A. Tybjaerg-Hansen, and B.G. Nordestgaard Total and cause-specific mortality by elevated transferrin saturation and hemochromatosis genotype in individuals with diabetes: two general population studies Diabetes Care 37 2014 444 452
91. C. Ellervik, A. Tybjaerg-Hansen, and B.G. Nordestgaard Risk of cancer by transferrin saturation levels and haemochromatosis genotype: population-based study and meta-analysis J Intern Med 271 2012 51 63
92. R.G. Stevens, B.I. Graubard, M.S. Micozzi, K. Neriishi, and B.S. Blumberg Moderate elevation of body iron level and increased risk of cancer occurrence and death International journal of cancer. Journal international du cancer 56 1994 364 369
93. A. Reunanen, H. Takkunen, P. Knekt, R. Seppanen, and A. Aromaa Body iron stores, dietary iron intake and coronary heart disease mortality J Intern Med 238 1995 223 230
94. L.W. Oberley Free radicals and diabetes Free Radic Biol Med 5 1988 113 124
95. C. Ellervik, T. Mandrup-Poulsen, H.U. Andersen, A. Tybjaerg-Hansen, M. Frandsen, H. Birgens, and B.G. Nordestgaard Elevated transferrin saturation and risk of diabetes: three population-based studies Diabetes Care 34 2011 2256 2258
96. E. Orban, S. Schwab, B. Thorand, and C. Huth Association of iron indices and type 2 diabetes: a meta-analysis of observational studies Diabetes/metabolism research and reviews 2013
97. W. Bao, Y. Rong, S. Rong, and L. Liu Dietary iron intake, body iron stores, and the risk of type 2 diabetes: a systematic review and meta-analysis BMC medicine 10 2012 119
98. R. Galanello, and R. Origa Beta-thalassemia Orphanet J Rare Dis 5 2010 11
99. C. Borgna-Pignatti, and M.R. Gamberini Complications of thalassemia major and their treatment Expert Rev Hematol 4 2011 353 366
100. F. Felicetti, F. D'Ascenzo, C. Moretti, A. Corrias, P. Omede, W.G. Marra, E. Arvat, F. Fagioli, E. Brignardello, and F. Gaita Prevalence of cardiovascular risk factors in long-term survivors of childhood cancer: 16 years follow up from a prospective registry European journal of preventive cardiology 2014
101. D. Hristozov, V. Gadjeva, T. Vlaykova, and G. Dimitrov Evaluation of oxidative stress in patients with cancer Archives of physiology and biochemistry 109 2001 331 336
102. H. Arai Oxidative modification of lipoproteins Sub-cellular biochemistry 77 2014 103 114
103. A. Menke, J.M. Fernandez-Real, P. Muntner, and E. Guallar The association of biomarkers of iron status with peripheral arterial disease in US adults BMC Cardiovasc Disord 9 2009 34
104. B.J. Wells, A.G. Mainous 3rd, D.E. King, J.M. Gill, P.J. Carek, and M.E. Geesey The combined effect of transferrin saturation and low density lipoprotein on mortality Family medicine 36 2004 324 329
105. A.G. Mainous 3rd, S.L. Eschenbach, B.J. Wells, C.J. Everett, and J.M. Gill Cholesterol, transferrin saturation, and the development of dementia and Alzheimer's disease: results from an 18-year population-based cohort Family medicine 37 2005 36 42
106. K. Farmaki, I. Tzoumari, C. Pappa, G. Chouliaras, and V. Berdoukas Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major Br J Haematol 148 2010 466 475
107. P.D. Jensen Iron overload in patients with myelodysplastic syndromes Current hematologic malignancy reports 2 2007 13 21
108. P.D. Jensen, L. Heickendorff, B. Pedersen, K. Bendix-Hansen, F.T. Jensen, T. Christensen, A.M. Boesen, and J. Ellegaard The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload Br J Haematol 94 1996 288 299
109. R. Guariglia, M.C. Martorelli, O. Villani, G. Pietrantuono, G. Mansueto, F. D'Auria, V. Grieco, G. Bianchino, R. Lerose, G.B. Bochicchio, and P. Musto Positive effects on hematopoiesis in patients with myelodysplastic syndrome receiving deferasirox as oral iron chelation therapy: a brief review Leuk Res 35 2011 566 570
110. H. Ghoti, E. Fibach, M. Westerman, O. Gordana, T. Ganz, and E.A. Rachmilewitz Increased serum hepcidin levels during treatment with deferasirox in iron-overloaded patients with myelodysplastic syndrome Br J Haematol 153 2011 118 120
111. E.N. Oliva, F. Ronco, A. Marino, C. Alati, G. Pratico, and F. Nobile Iron chelation therapy associated with improvement of hematopoiesis in transfusion-dependent patients Transfusion 50 2010 1568 1570
112. M.A. Badawi, L.M. Vickars, J.M. Chase, and H.A. Leitch Red blood cell transfusion independence following the initiation of iron chelation therapy in myelodysplastic syndrome Adv Hematol 2010 2010 164045
113. E. Messa, D. Cilloni, F. Messa, F. Arruga, A. Roetto, and G. Saglio Deferasirox treatment improved the hemoglobin level and decreased transfusion requirements in four patients with the myelodysplastic syndrome and primary myelofibrosis Acta Haematol 120 2008 70 74
114. N. Gattermann, C. Finelli, M. Della Porta, P. Fenaux, M. Stadler, A. Guerci-Bresler, M. Schmid, K. Taylor, D. Vassilieff, D. Habr, A. Marcellari, B. Roubert, and C. Rose Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes Haematologica 97 2012 1364 1371
115. J.W. Lee, P.S. Jang, N.G. Chung, B. Cho, D.C. Jeong, and H.K. Kim Iron chelation therapy with deferasirox results in recovery of hematopoiesis in a child with aplastic anemia Pediatr Hematol Oncol 28 2011 718 720
116. K.N. Koh, M. Park, B.E. Kim, H.J. Im, and J.J. Seo Restoration of hematopoiesis after iron chelation therapy with deferasirox in 2 children with severe aplastic anemia J Pediatr Hematol Oncol 32 2010 611 614
117. A.K. Bergmann, H. Tamary, and E.J. Neufeld Remission from transfusion-dependence in a patient with congenital dyserythropoietic anemia (CDA) and increased intensity of iron chelation Pediatr Blood Cancer 53 2009 1167 1168
118. W. Lu, M. Zhao, S. Rajbhandary, F. Xie, X. Chai, J. Mu, J. Meng, Y. Liu, Y. Jiang, X. Xu, and A. Meng Free iron catalyzes oxidative damage to hematopoietic cells/mesenchymal stem cells in vitro and suppresses hematopoiesis in iron overload patients Eur J Haematol 91 2013 249 261
119. K. Taoka, K. Kumano, F. Nakamura, M. Hosoi, S. Goyama, Y. Imai, A. Hangaishi, and M. Kurokawa The effect of iron overload and chelation on erythroid differentiation Int J Hematol 95 2012 149 159
120. S. Kikuchi, M. Kobune, S. Iyama, T. Sato, K. Murase, Y. Kawano, K. Takada, K. Ono, Y. Kaneko, K. Miyanishi, Y. Sato, T. Hayashi, R. Takimoto, and J. Kato Improvement of iron-mediated oxidative DNA damage in patients with transfusion-dependent myelodysplastic syndrome by treatment with deferasirox Free Radic Biol Med 53 2012 643 648
121. M. Schmid Iron chelation therapy in MDS: what have we learnt recently? Blood Rev 23 Suppl 1 2009 S21 25
122. N. Shenoy, N. Vallumsetla, E. Rachmilewitz, A. Verma, and Y. Ginzburg Impact of iron overload and potential benefit from iron chelation in low-risk myelodysplastic syndrome Blood 2014
123. M. Dussiot, T.T. Maciel, A. Fricot, C. Chartier, O. Negre, J. Veiga, D. Grapton, E. Paubelle, E. Payen, Y. Beuzard, P. Leboulch, J.A. Ribeil, J.B. Arlet, F. Cote, G. Courtois, Y.Z. Ginzburg, T.O. Daniel, R. Chopra, V. Sung, O. Hermine, and I.C. Moura An activin receptor IIA ligand trap corrects ineffective erythropoiesis in beta-thalassemia Nat Med 2014
124. Y.Z. Ginzburg, A.C. Rybicki, S.M. Suzuka, C.B. Hall, W. Breuer, Z.I. Cabantchik, E.E. Bouhassira, M.E. Fabry, and R.L. Nagel Exogenous iron increases hemoglobin in beta-thalassemic mice Exp Hematol 37 2009 172 183
125. L. Kautz, G. Jung, E.V. Valore, S. Rivella, E. Nemeth, and T. Ganz Identification of erythroferrone as an erythroid regulator of iron metabolism Nat Genet 2014
126. P. Ramos, C. Casu, S. Gardenghi, L. Breda, B.J. Crielaard, E. Guy, M.F. Marongiu, R. Gupta, R.L. Levine, O. Abdel-Wahab, B.L. Ebert, N. Van Rooijen, S. Ghaffari, R.W. Grady, P.J. Giardina, and S. Rivella Macrophages support pathological erythropoiesis in polycythemia vera and beta-thalassemia Nat Med 19 2013 437 445
127. L. Breda, C. Casu, S. Gardenghi, N. Bianchi, L. Cartegni, M. Narla, K. Yazdanbakhsh, M. Musso, D. Manwani, J. Little, L.B. Gardner, D.A. Kleinert, E. Prus, E. Fibach, R.W. Grady, P.J. Giardina, R. Gambari, and S. Rivella Therapeutic hemoglobin levels after gene transfer in beta-thalassemia mice and in hematopoietic cells of beta-thalassemia and sickle cells disease patients PLoS One 7 2012 e32345
128. S. Rivella Ineffective erythropoiesis and thalassemias Curr Opin Hematol 16 2009 187 194
129. S. Rivella The role of ineffective erythropoiesis in non-transfusion-dependent thalassemia Blood Rev 26 Suppl 1 2012 S12 15
130. S. Rivella, E. Nemeth, and J.L. Miller Crosstalk between Erythropoiesis and Iron Metabolism Adv Hematol 2010 2010
131. S. Gardenghi, M.F. Marongiu, P. Ramos, E. Guy, L. Breda, A. Chadburn, Y. Liu, N. Amariglio, G. Rechavi, E.A. Rachmilewitz, W. Breuer, Z.I. Cabantchik, D.M. Wrighting, N.C. Andrews, M. de Sousa, P.J. Giardina, R.W. Grady, and S. Rivella Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin Blood 109 2007 5027 5035
132. A.G. Mainous, R.J. Tanner, M.M. Hulihan, M. Amaya, and T.D. Coates The impact of chelation therapy on survival in transfusional iron overlaod: A meta-analysis of myelodysplastic syndrome Br J Haematol 2014
133. D. Farmakis, I. Andreadou, and A. Aessopos High-sensitivity troponin assays: ready for prime-time use as surrogates of subclinical myocardial injury? J Am Coll Cardiol 60 2012 166 (author reply 168)
134. M. Hatunic, F.M. Finucane, S. Norris, G. Pacini, and J.J. Nolan Glucose metabolism after normalization of markers of iron overload by venesection in subjects with hereditary hemochromatosis Metabolism 59 2010 1811 1815
135. J.B. Redmon, K.L. Pyzdrowski, and R.P. Robertson No effect of deferoxamine therapy on glucose homeostasis and insulin secretion in individuals with NIDDM and elevated serum ferritin Diabetes 42 1993 544 549
136. J.M. Fernandez-Real, G. Penarroja, A. Castro, F. Garcia-Bragado, I. Hernandez-Aguado, and W. Ricart Blood letting in high-ferritin type 2 diabetes: effects on insulin sensitivity and beta-cell function Diabetes 51 2002 1000 1004
137. J.B. Porter, R.D. Abeysinghe, L. Marshall, R.C. Hider, and S. Singh Kinetics of removal and reappearance of non-transferrin-bound plasma iron with deferoxamine therapy Blood 88 1996 705 713
138. Z.I. Cabantchik, W. Breuer, G. Zanninelli, and P. Cianciulli LPI-labile plasma iron in iron overload Best Pract Res Clin Haematol 18 2005 277 287
139. B.A. Davis, and J.B. Porter Long-term outcome of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in high-risk beta-thalassemia Blood 95 2000 1229 1236
140. M. Pandolfo, and L. Hausmann Deferiprone for the treatment of Friedreich's ataxia J Neurochem 126 Suppl 1 2013 142 146
141. D. Devos, C. Moreau, J.C. Devedjian, J. Kluza, M. Petrault, C. Laloux, A. Jonneaux, G. Ryckewaert, G. Garcon, N. Rouaix, A. Duhamel, P. Jissendi, K. Dujardin, F. Auger, L. Ravasi, L. Hopes, G. Grolez, W. Firdaus, B. Sablonniere, I. Strubi-Vuillaume, N. Zahr, A. Destee, J.C. Corvol, D. Poltl, M. Leist, C. Rose, L. Defebvre, P. Marchetti, Z.I. Cabantchik, and R. Bordet Targeting chelatable iron as a therapeutic modality in Parkinson's disease Antioxid Redox Signal 21 2014 195 210
142. M.M. Hudson, K.K. Ness, J.G. Gurney, D.A. Mulrooney, W. Chemaitilly, K.R. Krull, D.M. Green, G.T. Armstrong, K.A. Nottage, K.E. Jones, C.A. Sklar, D.K. Srivastava, and L.L. Robison Clinical ascertainment of health outcomes among adults treated for childhood cancer JAMA 309 2013 2371 2381
143. L.J. Noetzli, S.M. Carson, A.S. Nord, T.D. Coates, and J.C. Wood Longitudinal analysis of heart and liver iron in thalassemia major Blood 112 2008 2973 2978
144. M. Tukenova, I. Diallo, H. Anderson, M. Hawkins, S. Garwicz, R. Sankila, C. El Fayech, D. Winter, C. Rubino, E. Adjadj, N. Haddy, O. Oberlin, T. Moller, F. Langmark, L. Tryggvadottir, H. Pacquement, G. Svahn-Tapper, and F. de Vathaire Second malignant neoplasms in digestive organs after childhood cancer: a cohort-nested case-control study International journal of radiation oncology, biology, physics 82 2012 e383 390
145. P.D. Jensen, F.T. Jensen, T. Christensen, J.L. Nielsen, and J. Ellegaard Relationship between hepatocellular injury and transfusional iron overload prior to and during iron chelation with desferrioxamine: a study in adult patients with acquired anemias Blood 101 2003 91 96