Non-transfusion-dependent thalassemias

Haematologica

Volumn 98, Issue 6, 2013, Pages 833-844

  Musallam, Khaled M ^a   Rivella, Stefano ^b   Vichinsky, Elliott ^c   Rachmilewitz, Eliezer A ^d  

^a UNIVERSITY OF MILAN   (Italy)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

^c CHILDREN S HOSPITAL OAKLAND   (United States)

^d WOLFSON MEDICAL CENTER   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; DEFERASIROX; FERRITIN; HEMOGLOBIN A; HEMOGLOBIN ALPHA CHAIN; HEMOGLOBIN BETA CHAIN; HEMOGLOBIN E; HEMOGLOBIN H; HEPCIDIN; HYDROXYUREA; JANUS KINASE 2 INHIBITOR; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; RECOMBINANT ERYTHROPOIETIN; RUXOLITINIB; TRANSFERRIN;

ALPHA THALASSEMIA; BETA THALASSEMIA; BLOOD TRANSFUSION; BONE MARROW TRANSPLANTATION; DISEASE SEVERITY; ERYTHROID PRECURSOR CELL; ERYTHROPOIESIS; GENE DELETION; GENE THERAPY; GENOTYPE PHENOTYPE CORRELATION; HEMOLYSIS; HUMAN; HYPERCOAGULABILITY; IRON ABSORPTION; IRON CHELATION; IRON OVERLOAD; MORBIDITY; NONHUMAN; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SPLENECTOMY; SPLENOMEGALY; THALASSEMIA; VASCULAR DISEASE;

BLOOD TRANSFUSION; GENE-ENVIRONMENT INTERACTION; HUMANS; PHENOTYPE; THALASSEMIA;

EID: 84878455396     PISSN: 03906078     EISSN: 15928721     Source Type: Journal    
DOI: 10.3324/haematol.2012.066845     Document Type: Review

References (116)

1. Weatherall DJ, Clegg JB. The thalassaemia syndromes. 4th ed. Oxford: Blackwell Science; 2001.
2. Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood. 2011;118(13):3479-88.
3. Weatherall DJ. The definition and epidemiology of non-transfusion-dependent thalassemia. Blood Rev. 2012;(26 Suppl 1):S3-6.
4. Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010;115(22):4331-6.
5. Michlitsch J, Azimi M, Hoppe C, Walters MC, Lubin B, Lorey F, et al. Newborn screening for hemoglobinopathies in California. Pediatr Blood Cancer. 2009;52(4): 486-90.
6. Higgs DR, Engel JD, Stamatoyannopoulos G. Thalassaemia. Lancet. 2012;379(9813): 373-83.
7. Danjou F, Anni F, Galanello R. Beta-thalassemia: from genotype to phenotype. Haematologica. 2011;96(11):1573-5.
8. Galanello R. Recent advances in the molecular understanding of non-transfusion-dependent thalassemia. Blood Rev. 2012;26 (Suppl 1):S7-S11.
9. Weatherall D. 2003 William Allan Award address. The Thalassemias: the role of molecular genetics in an evolving global health problem. Am J Hum Genet. 2004; 74(3):385-92.
10. Galanello R, Piras S, Barella S, Leoni GB, Cipollina MD, Perseu L, et al. Cholelithiasis and Gilbert's syndrome in homozygous beta-thalassaemia. Br J Haematol. 2001;115 (4):926-8.
11. Graziadei G, Refaldi C, Barcellini W, Cesaretti C, Cassinero E, Musallam KM, et al. Does absolute excess of alpha chains compromise the benefit of splenectomy in patients with thalassemia intermedia? Haematologica. 2012;97(1):151-3.
12. Fucharoen S, Weatherall DJ. The hemoglobin e thalassemias. Cold Spring Harb Perspect Med. 2012;2(8).
13. Olivieri NF, Pakbaz Z, Vichinsky E. HbE/beta-thalassemia: basis of marked clinical diversity. Hematol Oncol Clin North Am. 2010;24(6):1055-70.
14. Olivieri NF, Muraca GM, O'Donnell A, Premawardhena A, Fisher C, Weatherall DJ. Studies in haemoglobin E beta-thalassaemia. Br J Haematol. 2008;141(3):388-97.
15. Sripichai O, Makarasara W, Munkongdee T, Kumkhaek C, Nuchprayoon I, Chuansumrit A, et al. A scoring system for the classification of beta-thalassemia/Hb E disease severity. Am J Hematol. 2008;83(6):482-4.
16. O'Donnell A, Premawardhena A, Arambepola M, Allen SJ, Peto TE, Fisher CA, et al. Age-related changes in adaptation to severe anemia in childhood in developing countries. Proc Natl Acad Sci USA. 2007;104(22):9440-4.
17. Allen A, Fisher C, Premawardhena A, Peto T, Allen S, Arambepola M, et al. Adaptation to anemia in hemoglobin E-ss thalassemia. Blood. 2010;116(24):5368-70.
18. Premawardhena A, Fisher CA, Olivieri NF, de Silva S, Arambepola M, Perera W, et al. Haemoglobin E beta thalassaemia in Sri Lanka. Lancet. 2005;366(9495):1467-70.
19. O'Donnell A, Premawardhena A, Arambepola M, Samaranayake R, Allen SJ, Peto TE, et al. Interaction of malaria with a common form of severe thalassemia in an Asian population. Proc Natl Acad Sci USA. 2009;106(44):18716-21.
20. Harteveld CL, Higgs DR. Alpha-thalassaemia. Orphanet J Rare Dis. 2010;5:13.
21. Higgs DR, Weatherall DJ. The alpha thalassaemias. Cell Mol Life Sci. 2009;66(7):1154-62.
22. Vichinsky E. Complexity of alpha thalassemia: growing health problem with new approaches to screening, diagnosis, and therapy. Ann NY Acad Sci. 2010;1202:180-7.
23. Singer ST, Kim HY, Olivieri NF, Kwiatkowski JL, Coates TD, Carson S, et al. Hemoglobin H-constant spring in North America: an alpha thalassemia with frequent complications. Am J Hematol. 2009; 84(11):759-61.
24. Vichinsky E. Advances in the treatment of alpha-thalassemia. Blood Rev. 2012;26 (Suppl 1):S31-4.
25. Lal A, Goldrich ML, Haines DA, Azimi M, Singer ST, Vichinsky EP. Heterogeneity of hemoglobin H disease in childhood. N Engl J Med. 2011;364(8):710-8.
26. Taher A, Isma'eel H, Cappellini MD. Thalassemia intermedia: revisited. Blood Cells Mol Dis. 2006;37(1):12-20.
27. Rivella S. The role of ineffective erythropoiesis in non-transfusion-dependent thalassemia. Blood Rev. 2012;26 (1 Suppl):S12-5.
28. Rivella S. Ineffective erythropoiesis and thalassemias. Curr Opin Hematol. 2009;16(3): 187-94.
29. Melchiori L, Gardenghi S, Rivella S. beta-Thalassemia: HiJAKing Ineffective Erythropoiesis and Iron Overload. Adv Hematol. 2010;2010:938640.
30. Taher AT, Musallam KM, Karimi M, El-Beshlawy A, Belhoul K, Daar S, et al. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study. Blood. 2010;115(10):1886-92.
31. Haidar R, Mhaidli H, Taher AT. Paraspinal extramedullary hematopoiesis in patients with thalassemia intermedia. Eur Spine J. 2010;19(6):871-8.
32. Musallam KM, Taher AT, Duca L, Cesaretti C, Halawi R, Cappellini MD. Levels of growth differentiation factor-15 are high and correlate with clinical severity in transfusion-independent patients with beta thalassemia intermedia. Blood Cells Mol Dis. 2011;47(4):232-4.
33. Gardenghi S, Marongiu MF, Ramos P, Guy E, Breda L, Chadburn A, et al. Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. Blood. 2007;109(11): 5027-35.
34. Ginzburg Y, Rivella S. beta-thalassemia: a model for elucidating the dynamic regulation of ineffective erythropoiesis and iron metabolism. Blood. 2011;118(16):4321-30.
35. Rivella S, Nemeth E, Miller JL. Crosstalk between Erythropoiesis and Iron Metabolism. Adv Hematol. 2010;2010. 317095.
36. Musallam KM, Cappellini MD, Taher AT. Iron overload in beta-thalassemia intermedia: an emerging concern. Curr Opin Hematol. 2013 Feb 18. [Epub ahead of print]
37. Musallam KM, Cappellini MD, Wood JC, Taher AT. Iron overload in non-transfusiondependent thalassemia: a clinical perspective. Blood Rev. 2012;26 (Suppl 1):S16-9.
38. Casanovas G, Vujic Spasic M, Casu C, Rivella S, Strelau J, Unsicker K, et al. The murine growth differentiation factor 15 is not essential for systemic iron homeostasis in phlebotomized mice. Haematologica. 2013;98(3):444-7.
39. Tanno T, Rabel A, Lee YT, Yau YY, Leitman SF, Miller JL. Expression of growth differentiation factor 15 is not elevated in individuals with iron deficiency secondary to volunteer blood donation. Transfusion. 2010;50(7): 1532-5.
40. Origa R, Galanello R, Ganz T, Giagu N, Maccioni L, Faa G, et al. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica. 2007;92(5):583-8.
41. Taher A, Musallam KM, El Rassi F, Duca L, Inati A, Koussa S, et al. Levels of non-transferrin-bound iron as an index of iron overload in patients with thalassaemia intermedia. Br J Haematol. 2009;146(5):569-72.
42. Taher AT, Porter J, Viprakasit V, Kattamis A, Chuncharunee S, Sutcharitchan P, et al. Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study. Blood. 2012;120(5):970-7.
43. Taher AT, Musallam KM, El-Beshlawy A, Karimi M, Daar S, Belhoul K, et al. Age-related complications in treatment-naive patients with thalassaemia intermedia. Br J Haematol. 2010;150(4):486-9.
44. Taher A, El Rassi F, Isma'eel H, Koussa S, Inati A, Cappellini MD. Correlation of liver iron concentration determined by R2 magnetic resonance imaging with serum ferritin in patients with thalassemia intermedia. Haematologica. 2008;93(10):1584-6.
45. Chen FE, Ooi C, Ha SY, Cheung BM, Todd D, Liang R, et al. Genetic and clinical features of hemoglobin H disease in Chinese patients. N Engl J Med. 2000;343(8):544-50.
46. Musallam KM, Cappellini MD, Wood JC, Motta I, Graziadei G, Tamim H, et al. Elevated liver iron concentration is a marker of increased morbidity in patients with beta thalassemia intermedia. Haematologica. 2011;96(11):1605-12.
47. Pakbaz Z, Fischer R, Fung E, Nielsen P, Harmatz P, Vichinsky E. Serum ferritin underestimates liver iron concentration in transfusion independent thalassemia patients as compared to regularly transfused thalassemia and sickle cell patients. Pediatr Blood Cancer. 2007;49(3):329-32.
48. Musallam KM, Motta I, Salvatori M, Fraquelli M, Marcon A, Taher AT, et al. Longitudinal changes in serum ferritin levels correlate with measures of hepatic stiffness in transfusion-independent patients with beta-thalassemia intermedia. Blood Cells Mol Dis. 2012;49(3-4):136-9.
49. Maakaron JE, Cappellini MD, Graziadei G, Ayache JB, Taher AT. Hepatocellular carcinoma in hepatitis-negative patients with thalassemia intermedia: a closer look at the role of siderosis. Ann Hepatol. 2013;12(1):142-6.
50. Origa R, Barella S, Argiolas GM, Bina P, Agus A, Galanello R. No evidence of cardiac iron in 20 never-or minimally-transfused patients with thalassemia intermedia. Haematologica. 2008;93(7):1095-6.
51. Taher AT, Musallam KM, Wood JC, Cappellini MD. Magnetic resonance evaluation of hepatic and myocardial iron deposition in transfusion-independent thalassemia intermedia compared to regularly transfused thalassemia major patients. Am J Hematol. 2010;85(4):288-90.
52. Roghi A, Cappellini MD, Wood JC, Musallam KM, Patrizia P, Fasulo MR, et al. Absence of cardiac siderosis despite hepatic iron overload in Italian patients with thalassemia intermedia: an MRI T2* study. Ann Hematol. 2010;89(6):585-9.
53. Mavrogeni S, Gotsis E, Ladis V, Berdousis E, Verganelakis D, Toulas P, et al. Magnetic resonance evaluation of liver and myocardial iron deposition in thalassemia intermedia and b-thalassemia major. Int J Cardiovasc Imaging. 2008;24(8):849-54.
54. Musallam KM, Cappellini MD, Taher AT. Evaluation of the 5mg/g liver iron concentration threshold and its association with morbidity in patients with beta-thalassemia intermedia. Blood Cells Mol Dis. 2013;51 (1):35-8.
55. Ziyadeh FN, Musallam KM, Mallat NS, Mallat S, Jaber F, Mohamed AA, et al. Glomerular Hyperfiltration and Proteinuria in Transfusion-Independent Patients with beta-Thalassemia Intermedia. Nephron Clin Pract. 2012;121(3-4):c136-c43.
56. Eldor A, Durst R, Hy-Am E, Goldfarb A, Gillis S, Rachmilewitz EA, et al. A chronic hypercoagulable state in patients with betathalassaemia major is already present in childhood. Br J Haematol. 1999;107(4):739-46.
57. Eldor A, Rachmilewitz EA. The hypercoagulable state in thalassemia. Blood. 2002;99(1):36-43.
58. Cappellini MD, Musallam KM, Poggiali E, Taher AT. Hypercoagulability in non-transfusion-dependent thalassemia. Blood Rev. 2012;26 (1 Suppl):S20-3.
59. Ataga KI, Cappellini MD, Rachmilewitz EA. Beta-thalassaemia and sickle cell anaemia as paradigms of hypercoagulability. Br J Haematol. 2007;139(1):3-13.
60. Musallam KM, Taher AT. Thrombosis in thalassemia: why are we so concerned? Hemoglobin. 2011;35(5-6):503-10.
61. Cappellini MD, Motta I, Musallam KM, Taher AT. Redefining thalassemia as a hypercoagulable state. Ann NY Acad Sci. 2010;1202:231-6.
62. Borgna Pignatti C, Carnelli V, Caruso V, Dore F, De Mattia D, Di Palma A, et al. Thromboembolic events in beta thalassemia major: an Italian multicenter study. Acta Haematol. 1998;99(2):76-9.
63. Cappellini MD, Robbiolo L, Bottasso BM, Coppola R, Fiorelli G, Mannucci AP. Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia. Br J Haematol. 2000;111 (2):467-73.
64. Taher A, Isma'eel H, Mehio G, Bignamini D, Kattamis A, Rachmilewitz EA, et al. Prevalence of thromboembolic events among 8,860 patients with thalassaemia major and intermedia in the Mediterranean area and Iran. Thromb Haemost. 2006;96 (4):488-91.
65. Taher AT, Musallam KM, Karimi M, El-Beshlawy A, Belhoul K, Daar S, et al. Splenectomy and thrombosis: the case of thalassemia intermedia. J Thromb Haemost. 2010;8(10):2152-8.
66. Musallam KM, Taher AT, Karimi M, Rachmilewitz EA. Cerebral infarction in beta-thalassemia intermedia: Breaking the silence. Thromb Res. 2012;130(5):695-702.
67. Musallam KM, Nasreddine W, Beydoun A, Hourani R, Hankir A, Koussa S, et al. Brain positron emission tomography in splenectomized adults with beta-thalassemia intermedia: uncovering yet another covert abnormality. Ann Hematol. 2012;91(2):235-41.
68. Musallam KM, Beydoun A, Hourani R, Nasreddine W, Raad R, Koussa S, et al. Brain magnetic resonance angiography in splenectomized adults with beta-thalassemia inter-media. Eur J Haematol. 2011;87(6):539-46.
69. Farmakis D, Aessopos A. Pulmonary hypertension associated with hemoglobinopathies: prevalent but overlooked. Circulation. 2011;123(11):1227-32.
70. Parent F, Bachir D, Inamo J, Lionnet F, Driss F, Loko G, et al. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med. 2011;365(1):44-53.
71. Musallam KM, Taher AT, Rachmilewitz EA. beta-Thalassemia Intermedia: A Clinical Perspective. Cold Spring Harb Perspect Med. 2012;2(7):a013482.
72. Morris CR, Vichinsky EP. Pulmonary hypertension in thalassemia. Ann NY Acad Sci. 2010;1202:205-13.
73. Morris CR, Kim H-Y, Wood JC, Trachtenberg F, Klings ES, Porter JB, et al. Sildenafil therapy in patients with thalassemia and an elevated tricuspid regurgitant jet velocity (TRV) on doppler echocardiography at risk for pulmonary hypertension: report from the thalassemia clinical research network. Blood. 2012;120 (21):1023.
74. Morris CR, Kim H-Y, Wood JC, Trachtenberg F, Klings ES, Porter JB, et al. Cardiopulmonary and laboratory profiling of patients with thalassemia at risk for pulmonary hypertension: report from the thalassemia clinical research network. Blood. 2012;120(21):2122.
75. Morris CR, Kuypers FA, Kato GJ, Lavrisha L, Larkin S, Singer T, et al. Hemolysis-associated pulmonary hypertension in thalassemia. Ann NY Acad Sci. 2005;1054:481-5.
76. Musallam KM, Sankaran VG, Cappellini MD, Duca L, Nathan DG, Taher AT. Fetal hemoglobin levels and morbidity in untransfused patients with beta-thalassemia intermedia. Blood. 2012;119(2):364-7.
77. Levin C, Koren A. Healing of refractory leg ulcer in a patient with thalassemia intermedia and hypercoagulability after 14 years of unresponsive therapy. Isr Med Assoc J. 2011;13(5):316-8.
78. Musallam KM, Khoury B, Abi-Habib R, Bazzi L, Succar J, Halawi R, et al. Healthrelated quality of life in adults with transfusion-independent thalassaemia intermedia compared to regularly transfused thalassaemia major: new insights. Eur J Haematol. 2011;87(1):73-9.
79. Pakbaz Z, Treadwell M, Yamashita R, Quirolo K, Foote D, Quill L, et al. Quality of life in patients with thalassemia intermedia compared to thalassemia major. Ann N Y Acad Sci. 2005;1054:457-61.
80. Taher AT, Musallam KM, Cappellini MD, Weatherall DJ. Optimal management of beta thalassaemia intermedia. Br J Haematol. 2011;152(5):512-23.
81. Tso SC, Chan TK, Todd D. Venous thrombosis in haemoglobin H disease after splenectomy. Aust NZ J Med. 1982;12(6): 635-8.
82. Mannu F, Arese P, Cappellini MD, Fiorelli G, Cappadoro M, Giribaldi G, et al. Role of hemichrome binding to erythrocyte membrane in the generation of band-3 alterations in beta-thalassemia intermedia erythrocytes. Blood. 1995;86(5):2014-20.
83. Taher AT, Musallam KM, Karimi M, Cappellini MD. Contemporary approaches to treatment of beta-thalassemia intermedia. Blood Rev. 2012;26 (Suppl 1):S24-7.
84. Olivieri NF. Treatment strategies for hemoglobin E beta-thalassemia. Blood Rev. 2012;26 (Suppl 1):S28-30.
85. Karimi M, Musallam KM, Cappellini MD, Daar S, El-Beshlawy A, Belhoul K, et al. Risk factors for pulmonary hypertension in patients with beta thalassemia intermedia. Eur J Intern Med. 2011;22(6):607-10.
86. Taher AT, Musallam KM, Nasreddine W, Hourani R, Inati A, Beydoun A. Asymptomatic brain magnetic resonance imaging abnormalities in splenectomized adults with thalassemia intermedia. J Thromb Haemost. 2010;8(1):54-9.
87. Kosaryan M, Mahdavi MR, Roshan P, Hojjati MT. Prevalence of alloimmunisation in patients with beta thalassaemia major. Blood Transfus. 2012;10(3):396-7.
88. Chou ST, Liem RI, Thompson AA. Challenges of alloimmunization in patients with haemoglobinopathies. Br J Haematol. 2012;159(4):394-404.
89. Musallam KM, Cappellini MD, Daar S, Karimi M, El-Beshlawy A, Taher AT. Serum ferritin levels and morbidity in f-thalassemia intermedia: a 10-year cohort study. Blood. 2012;120(21):1021.
90. Taher A, Porter J, Viprakasit V, Kattamis A, Chuncharunee S, Sutcharitchan P, et al. Estimation of liver iron concentration by serum ferritin measurement in non-transfusion-dependent thalassemia patients: analysis from the 1-year THALASSA study. Haematologica. 2012;96(S1):0927.
91. Taher AT, Porter JB, Viprakasit V, Kattamis A, Chuncharunee S, Sutcharitchan P, et al. Deferasirox continues to reduce iron overload in non-transfusion-dependent thalassemia: a one-year, open-label extension to a one-year, randomized, double-blind, placebo-controlled study (THALASSA). Blood. 2012;120(21):3258.
92. Cossu P, Toccafondi C, Vardeu F, Sanna G, Frau F, Lobrano R, et al. Iron overload and desferrioxamine chelation therapy in betathalassemia intermedia. Eur J Pediatr. 1981;137(3):267-71.
93. Olivieri NF, Koren G, Matsui D, Liu PP, Blendis L, Cameron R, et al. Reduction of tissue iron stores and normalization of serum ferritin during treatment with the oral iron chelator L1 in thalassemia intermedia. Blood. 1992;79(10):2741-8.
94. Pippard MJ, Weatherall DJ. Iron balance and the management of iron overload in betathalassemia intermedia. Birth Defects Orig Artic Ser. 1988;23(5B):29-33.
95. Nuinoon M, Makarasara W, Mushiroda T, Setianingsih I, Wahidiyat PA, Sripichai O, et al. A genome-wide association identified the common genetic variants influence disease severity in beta0-thalassemia/hemoglobin E. Hum Genet. 2010;127(3):303-14.
96. Galanello R, Sanna S, Perseu L, Sollaino MC, Satta S, Lai ME, et al. Amelioration of Sardinian beta0 thalassemia by genetic modifiers. Blood. 2009;114(18):3935-7.
97. Danjou F, Anni F, Perseu L, Satta S, Dessi C, Lai ME, et al. Genetic modifiers of beta-thalassemia and clinical severity as assessed by age at first transfusion. Haematologica. 2012;97(7):989-93.
98. Badens C, Joly P, Agouti I, Thuret I, Gonnet K, Fattoum S, et al. Variants in genetic modifiers of beta-thalassemia can help to predict the major or intermedia type of the disease. Haematologica. 2011;96(11):1712-4.
99. Uda M, Galanello R, Sanna S, Lettre G, Sankaran VG, Chen W, et al. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. Proc Natl Acad Sci USA. 2008;105(5):1620-5.
100. Ma Q, Abel K, Sripichai O, Whitacre J, Angkachatchai V, Makarasara W, et al. Betaglobin gene cluster polymorphisms are strongly associated with severity of HbE/beta(0)-thalassemia. Clin Genet. 2007; 72(6):497-505.
101. Musallam KM, Taher AT, Cappellini MD, Sankaran VG. Clinical experience with fetal hemoglobin induction therapy in patients with beta-thalassemia. Blood. 2013 Mar 21;121(12):2199-212; quiz 2372.
102. Olivieri NF, Saunthararajah Y, Thayalasuthan V, Kwiatkowski J, Ware RE, Kuypers FA, et al. A pilot study of subcutaneous decitabine in beta-thalassemia intermedia. Blood. 2011;118 (10):2708-11.
103. Singer ST, Vichinsky EP, Larkin S, Olivieri N, Sweeters N, Kuypers FA. Hydroxycarbamide-induced changes in E/beta thalassemia red blood cells. Am J Hematol. 2008;83(11):842-5.
104. Singer ST, Vichinsky EP, Sweeters N, Rachmilewitz E. Darbepoetin alfa for the treatment of anaemia in alpha-or beta-thalassaemia intermedia syndromes. Br J Haematol. 2011;154(2):281-4.
105. Rivella S, Rachmilewitz E. Future alternative therapies for beta-thalassemia. Expert Rev Hematol. 2009;2(6):685.
106. Libani IV, Guy EC, Melchiori L, Schiro R, Ramos P, Breda L, et al. Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in beta-thalassemia. Blood. 2008;112(3):875-85.
107. Melchiori L, Gardenghi S, Guy EG, Rachmilewitz E, Giardina PJ, Grady RW, et al. Use of JAK2 inhibitors to limit ineffective erythropoiesis and iron absorption in mice affected by f-thalassemia and other disorders of red cell production [abstract]. Blood. 2009;114(22):2020.
108. Tefferi A. JAK inhibitors for myeloproliferative neoplasms: clarifying facts from myths. Blood. 2012;119(12):2721-30.
109. Gardenghi S, Ramos P, Marongiu MF, Melchiori L, Breda L, Guy E, et al. Hepcidin as a therapeutic tool to limit iron overload and improve anemia in beta-thalassemic mice. J Clin Invest. 2010;120(12):4466-77.
110. Nai A, Pagani A, Mandelli G, Lidonnici MR, Silvestri L, Ferrari G, et al. Deletion of TMPRSS6 attenuates the phenotype in a mouse model of beta-thalassemia. Blood. 2012;119(21):5021-9.
111. Parrow NL, Gardenghi S, Rivella S. Prospects for a hepcidin mimic to treat beta-thalassemia and hemochromatosis. Expert Rev Hematol. 2011;4(3):233-5.
112. Ramos E, Ruchala P, Goodnough JB, Kautz L, Preza GC, Nemeth E, et al. Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe hemochromatosis. Blood. 2012;120(18):3829-36.
113. Preza GC, Ruchala P, Pinon R, Ramos E, Qiao B, Peralta MA, et al. Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload. J Clin Invest. 2011;121(12):4880-8.
114. Li H, Rybicki AC, Suzuka SM, von Bonsdorff L, Breuer W, Hall CB, et al. Transferrin therapy ameliorates disease in beta-thalassemic mice. Nat Med. 2010;16(2): 177-82.
115. Sankaran VG. Targeted therapeutic strategies for fetal hemoglobin induction. Hematology Am Soc Hematol Educ Program. 2011;2011:459-65.
116. Xu J, Peng C, Sankaran VG, Shao Z, Esrick EB, Chong BG, et al. Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. Science. 2011;334(6058):993-6.