Artículos de revistas
The Genetics Of Blood Disorders: Hereditary Hemoglobinopathies
Registro en:
Jornal De Pediatria. , v. 84, n. 4 SUPPL., p. S40 - S51, 2008.
217557
10.2223/JPED.1802
2-s2.0-57349187681
Autor
De Sonati M.F.
Costa F.F.
Institución
Resumen
Objective: To summarize recently published data on the pathophysiology, diagnosis and treatment of sickle cell diseases and β-Thalassemias, the most relevant hereditary hemoglobinopathies in the global population. Sources: Searches were run on the MEDLINE and SCIELO databases, limited to the period from 2003 to May 2008, using the terms hereditary hemoglobinopathies, sickle cell diseases and β-thalassemia. Two books and two chapters were also included. Summary of the findings: More than 2,000 articles were identified; those providing the most important information and broadest views were selected. Conclusions: Morbidity and mortality rates from sickle cell diseases and β-thalassemia are still very high and represent an important challenge. Increased understanding of pathophysiological aspects has lead to significant improvements in treatment and prevention of these diseases. Copyright © 2008 by Sociedade Brasileira de Pediatria. 84 4 SUPPL. S40 S51 Steiner, L.A., Gallagher, P.G., Erythrocyte disorders in the perinatal period (2007) Semin Perinatol, 31, pp. 254-261 Tolentino, K., Friedman, J.F., An update on anemia in less developed countries (2007) Am J Trop Med Hyg, 77, pp. 44-51 (2004) Wintrobe's clinical hematology, , Wintrobe MM, Foerster J, editors, 11th ed. Philadelphia: Lippincott Williams & Wilkins; Dhaliwal, G., Cornett, P.A., Tierney Jr., L.M., Hemolytic anemia (2004) Am Fam Physician, 69, pp. 2599-2606 Madigan, C., Malik, P., Pathophysiology and therapy for haemoglobinopathies. Part I: Sickle cell disease (2006) Expert Rev Mol Med, 8, pp. 1-23 Urbinati, F., Madigan, C., Malik, P., Pathophysiology and therapy for haemoglobinopathies. Part II: Thalassaemias (2006) Expert Rev Mol Med, 8, pp. 1-26 Old, J.M., Screening and genetic diagnosis of haemoglobinopathies (2007) Scand J Clin Lab Invest, 67, pp. 71-86 Khattab, A.D., Rawlings, B., Ali, I.S., Care of patients with haemoglobin abnormalities: History and biology (2006) Br J Nurs, 15, pp. 994-998 Theodorsson, E., Birgens, H., Hagve, T.A., Haemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency in a Scandinavian perspective (2007) Scand J Clin Lab Invest, 67, pp. 3-10 Morris, C.R., Singer, S.T., Walters, M.C., Clinical hemoglobinopathies: Iron, lungs and new blood (2006) Curr Opin Hematol, 13, pp. 407-418 (2004) Hematologia: Fundamentos e prática, , Zago MA, Falcão RP, Pasquini R, editors, São Paulo: Atheneu; Costa, F.F., Sonati, M.F., Hemoglobina: Estrutura, síntese e transporte de oxigênio (2007) Hemoterapia: Fundamentos e prática, pp. 27-33. , Covas DT, Langhi Júnior DM, Bordin JO, editors, São Paulo: Atheneu; Wenning, M.R., Sonati, M.F., Hemoglobinopatias hereditárias (2007) Diagnóstico e tratamento, pp. 310-314. , Lopes AC, editor, São Paulo: Manole; Vekilov, P.G., Sickle-cell haemoglobin polymerization: Is it the primary pathogenic event of sickle-cell anaemia? (2007) Br J Haematol, 139, pp. 173-184 Tefferi, A., Clinical, genetic, and therapeutic insights into systemic mast cell disease (2004) Curr Opin Hematol, 11, pp. 58-64 Catlin, A.J., Thalassemia: The facts and the controversies (2003) Pediatr Nurs, 29, pp. 447-449 Thein, S.L., Genetic insights into the clinical diversity of beta thalassaemia (2004) Br J Haematol, 124, pp. 264-274 Shah, A., Thalassemia syndromes (2004) Indian J Med Sci, 58, pp. 445-449 Williams, T.N., Human red blood cell polymorphisms and malaria (2006) Curr Opin Microbiol, 9, pp. 388-394 Williams, T.N., Red blood cell defects and malaria (2006) Mol Biochem Parasitol, 149, pp. 121-127 Frenette, P.S., Atweh, G.F., Sickle cell disease: Old discoveries, new concepts, and future promise (2007) J Clin Invest, 117, pp. 850-858 Di Nuzzo, D.V., Fonseca, S.F., Sickle cell disease and infection] (2004) J Pediatr (Rio J), 80, pp. 347-354 Lyra, I.M., Gonçalves, M.S., Braga, J.A., MdeF, G., Carvalho, M.H., Saad, S.T., Clinical, hematological, and molecular characterization of sickle cell anemia pediatric patients from two different cities in Brazil (2005) Cad Saude Publica, 21, pp. 1287-1290 Lima, C.S., Rocha, E.M., Silva, N.M., Sonatti, M.F., Costa, F.F., Saad, S.T., Risk factors for conjunctival and retinal vessel alterations in sickle cell disease (2006) Acta Ophthalmol Scand, 84, pp. 234-241 Adams, R.J., Big strokes in small persons (2007) Arch Neurol, 64, pp. 1567-1574 Brittain, J.E., Parise, L.V., Cytokines and plasma factors in sickle cell disease (2007) Curr Opin Hematol, 14, pp. 438-443 Seidman, C., Kirkham, F., Pavlakis, S., Pediatric stroke: Current developments (2007) Curr Opin Pediatr, 19, pp. 657-662 Traina, F., Jorge, S.G., Yamanaka, A., de Meirelles, L.R., Costa, F.F., Saad, S.T., Chronic liver abnormalities in sickle cell disease: A clinicopathological study in 70 living patients (2007) Acta Haematol, 118, pp. 129-135 Wong, W.Y., Powars, D.R., Overt and incomplete (silent) cerebral infarction in sickle cell anemia: Diagnosis and management (2007) Neuroimaging Clin N Am, 17, pp. 269-280 Creary, M., Williamson, D., Kulkarni, R., Sickle cell disease: Current activities, public health implications, and future directions (2007) J Womens Health (Larchmt), 16, pp. 575-582 Castro, O., Hoque, M., Brown, B.D., Pulmonary hypertension in sickle cell disease: Cardiac catheterization results and survival (2003) Blood, 101, pp. 1257-1261 Ataga, K.I., Sood, N., De Gent, G., Kelly, E., Henderson, A.G., Jones, S., Pulmonary hypertension in sickle cell disease (2004) Am J Med, 117, pp. 665-669 Machado, R.F., Gladwin, M.T., Chronic sickle cell lung disease: New insights into the diagnosis, pathogenesis and treatment of pulmonary hypertension (2005) Br J Haematol, 129, pp. 449-464 Morris, C.R., Kato, G.J., Poljakovic, M., Wang, X., Blackwelder, W.C., Sachdev, V., Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease (2005) JAMA, 294, pp. 81-90 Kato, G.J., Onyekwere, O.C., Gladwin, M.T., Pulmonary hypertension in sickle cell disease: Relevance to children (2007) Pediatr Hematol Oncol, 24, pp. 159-170 Barnett, C.F., Hsue, P.Y., Machado, R.F., Pulmonary hypertension: An increasingly recognized complication of hereditary hemolytic anemias and HIV infection (2008) JAMA, 299, pp. 324-331 Claster, S., Vichinsky, E.P., Managing sickle cell disease (2003) BMJ, 327, pp. 1151-1155 Berry, P.A., Cross, T.J., Thein, S.L., Portmann, B.C., Wendon, J.A., Karani, J.B., Hepatic dysfunction in sickle cell disease: A new system of classification based on global assessment (2007) Clin Gastroenterol Hepatol, 5, pp. 1469-1476 Adorno, E.V., Couto, F.D., Moura Neto, J.P., Menezes, J.F., Rêgo, M., Reis, M.G., Gonçalves, M.S., Hemoglobinopathies in newborns from Salvador, Bahia, Northeast Brazil (2005) Cad Saude Publica, 21, pp. 292-298 Chiang, E.Y., Frenette, P.S., Sickle cell vaso-occlusion (2005) Hematol Oncol Clin North Am, 19, pp. 771-784 Joiner, C.H., Rettig, R.K., Jiang, M., Franco, R.S., KCl cotransport mediates abnormal sulfhydryl-dependent volume regulation in sickle reticulocytes (2004) Blood, 104, pp. 2954-2960 Lew, V.L., Bookchin, R.M., Ion transport pathology in the mechanism of sickle cell dehydration (2005) Physiol Rev, 85, pp. 179-200 Zen Q, Batchvarova M, Twyman CA, Eyler CE, Qiu H, De Castro LM, Telen MJ. B-CAM/LU expression and the role of B-CAM/LU activation in binding of low- and high-density red cells to laminin in sickle cell disease. Am J Hematol. 2004;75:63-7Assis, A., Conran, N., Canalli, A.A., Lorand-Metze, I., Saad, S.T., Costa, F.F., Effect of cytokines and chemokines on sickle neutrophil adhesion to fibronectin (2005) Acta Haematol, 113, pp. 130-136 Canalli, A.A., Costa, F.F., Saad, S.T., Conran, N., Granulocytic adhesive interactions and their role in sickle cell vaso-occlusion (2005) Hematology, 10, pp. 419-425 Conran, N., Saad, S.T., Costa, F.F., Ikuta, T., Leukocyte numbers correlate with plasma levels of granulocyte-macrophage colony-stimulating factor in sickle cell disease (2007) Ann Hematol, 86, pp. 255-261 Canalli, A.A., Franco-Penteado, C.F., Traina, F., Saad, S.T., Costa, F.F., Conran, N., Role for cAMP-protein kinase A signalling in augmented neutrophil adhesion and chemotaxis in sickle cell disease (2007) Eur J Haematol, 79, pp. 330-337 Conran, N., Almeida, C.B., Lanaro, C., Ferreira, R.P., Traina, F., Saad, S.T., Inhibition of caspase-dependent spontaneous apoptosis via a cAMP-protein kinase A dependent pathway in neutrophils from sickle cell disease patients (2007) Br J Haematol, 139, pp. 148-158 Canalli, A.A., Conran, N., Fattori, A., Saad, S.T., Costa, F.F., Increased adhesive properties of eosinophils in sickle cell disease (2004) Exp Hematol, 32, pp. 728-734 Belcher, J.D., Bryant, C.J., Nguyen, J., Bowlin, P.R., Kielbik, M.C., Bischof, J.C., Transgenic sickle mice have vascular inflammation (2003) Blood, 101, pp. 3953-3959 Perelman, N., Selvaraj, S.K., Batra, S., Luck, L.R., Erdreich-Epstein, A., Coates, T.D., Placenta growth factor activates monocytes and correlates with sickle cell disease severity (2003) Blood, 102, pp. 1506-1514 Solovey, A., Kollander, R., Shet, A., Milbauer, L.C., Choong, S., Panoskaltsis-Mortari, A., Endothelial cell expression of tissue factor in sickle mice is augmented by hypoxia/reoxygenation and inhibited by lovastatin (2004) Blood, 104, pp. 840-846 Aslan, M., Freeman, B.A., Redox-dependent impairment of vascular function in sickle cell disease (2007) Free Radic Biol Med, 43, pp. 1469-1483 Conran, N., Gambero, A., Ferreira, H.H., Antunes, E., de Nucci, G., Nitric oxide has a role in regulating VLA-4-integrin expression on the human neutrophil cell surface (2003) Biochem Pharmacol, 66, pp. 43-50 Kaul, D.K., Liu, X.D., Chang, H.Y., Nagel, R.L., Fabry, M.E., Effect of fetal hemoglobin on microvascular regulation in sickle transgenic-knockout mice (2004) J Clin Invest, 114, pp. 1136-1145 Steinberg, M.H., Predicting clinical severity in sickle cell anaemia (2005) Br J Haematol, 129, pp. 465-481 Fathallah, H., Atweh, G.F., (2006) Induction of fetal hemoglobin in the treatment of sickle cell disease, pp. 58-62. , Hematology Am Soc Hematol Educ Program Adorno, E.V., Zanette, A., Lyra, I., Souza, C.C., Santos, L.F., Menezes, J.F., The beta-globin gene cluster haplotypes in sickle cell anemia patients from Northeast Brazil: A clinical and molecular view (2004) Hemoglobin, 28, pp. 267-271 Hoppe, C., Klitz, W., Noble, J., Vigil, L., Vichinsky, E., Styles, L., Distinct HLA associations by stroke subtype in children with sickle cell anemia (2003) Blood, 101, pp. 2865-2869 Sebastiani, P., Ramoni, M.F., Nolan, V., Baldwin, C.T., Steinberg, M.H., Genetic dissection and prognostic modeling of overt stroke in sickle cell anemia (2005) Nat Genet, 37, pp. 435-440 Castro, V., Alberto, F.L., Costa, R.N., Lepikson-Neto, J., Gualandro, S.F., Figueiredo, M.S., Polymorphism of the human platelet antigen-5 system is a risk factor for occlusive vascular complications in patients with sickle cell anemia (2004) Vox Sang, 87, pp. 118-123 Steinberg, M.H., Adewoye, A.H., Modifier genes and sickle cell anemia (2006) Curr Opin Hematol, 13, pp. 131-136 Kutlar, F., Diagnostic approach to hemoglobinopathies (2007) Hemoglobin, 31, pp. 243-250 Colah, R.B., Surve, R., Sawant, P., D'Souza, E., Italia, K., Phanasgaonkar, S., HPLC studies in hemoglobinopathies (2007) Indian J Pediatr, 74, pp. 657-662 Cremonesi, L., Ferrari, M., Giordano, P.C., Harteveld, C.L., Kleanthous, M., Papasavva, T., An overview of current microarray-based human globin gene mutation detection methods (2007) Hemoglobin, 31, pp. 289-311 Kutlar, A., Sickle cell disease: A multigenic perspective of a single gene disorder (2007) Hemoglobin, 31, pp. 209-224 Steinberg, M.H., Barton, F., Castro, O., Pegelow, C.H., Ballas, S.K., Kutlar, A., Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: Risks and benefits up to 9 years of treatment (2003) JAMA, 289, pp. 1645-1651 Davies, S.C., Gilmore, A., The role of hydroxyurea in the management of sickle cell disease (2003) Blood Rev, 17, pp. 99-109 Conran, N., Fattori, A., Saad, S.T., Costa, F.F., Increased levels of soluble ICAM-1 in the plasma of sickle cell patients are reversed by hydroxyurea (2004) Am J Hematol, 76, pp. 343-347 De Franceschi, L., Corrocher, R., Established and experimental treatments for sickle cell disease (2004) Haematologica, 89, pp. 348-356 Gambero, S., Canalli, A.A., Traina, F., Albuquerque, D.M., Saad, S.T., Costa, F.F., Conran, N., Therapy with hydroxyurea is associated with reduced adhesion molecule gene and protein expression in sickle red cells with a concomitant reduction in adhesive properties (2007) Eur J Haematol, 78, pp. 144-151 Haynes Jr, J., Obiako, B., Hester, R.B., Baliga, B.S., Stevens, T., Hydroxyurea attenuates activated neutrophil-mediated sickle erythrocyte membrane phosphatidylserine exposure and adhesion to pulmonary vascular endothelium (2008) Am J Physiol Heart Circ Physiol, 294, pp. H379-H385 Johnson, C., Telen, M.J., Adhesion molecules and hydroxyurea in the pathophysiology of sickle cell disease (2008) Haematologica, 93, pp. 481-485 Moreira, L.S., de Andrade, T.G., Albuquerque, D.M., Cunha, A.F., Fattori, A., Saad, S.T., Costa, F.F., Identification of differentially expressed genes induced by hydroxyurea in reticulocytes from sickle cell anaemia patients (2008) Clin Exp Pharmacol Physiol, 35, pp. 651-655 Fattori, A., de Souza, R.A., Saad, S.T., Costa, F.F., Acute myocardial infarction in sickle cell disease: A possible complication of hydroxyurea treatment (2005) Hematol J, 5, pp. 589-590 Steinberg, M.H., Brugnara, C., Pathophysiological-based approaches to treatment of sickle cell disease (2003) Annu Rev Med, 54, pp. 89-112 Locatelli, F., Rocha, V., Reed, W., Bernaudin, F., Ertem, M., Grafakos, S., Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease (2003) Blood, 101, pp. 2137-2143 Cheung, A.T., Chan, M.S., Ramanujam, S., Rangaswami, A., Curl, K., Franklin, P., Effects of poloxamer 188 treatment on sickle cell vaso-occlusive crisis: Computer-assisted intravital microscopy study (2004) J Investig Med, 52, pp. 402-406 Makis, A.C., Hatzimichael, E.C., Stebbing, J., The genomics of new drugs in sickle cell disease (2006) Pharmacogenomics, 7, pp. 909-917 Stocker, J.W., De Franceschi, L., McNaughton-Smith, G.A., Corrocher, R., Beuzard, Y., Brugnara, C., ICA-17043, a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice (2003) Blood, 101, pp. 2412-2418 Mack, A.K., Kato, G.J., Sickle cell disease and nitric oxide: A paradigm shift? (2006) Int J Biochem Cell Biol, 38, pp. 1237-1243 Machado, R.F., Martyr, S., Kato, G.J., Barst, R.J., Anthi, A., Robinson, M.R., Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension (2005) Br J Haematol, 130, pp. 445-453 Canalli, A.A., Franco-Penteado, C.F., Saad, S.T., Conran, N., Costa, F.F., Increased adhesive properties of neutrophils in sickle cell disease may be reversed by pharmacological nitric oxide donation (2008) Haematologica, 93, pp. 605-609 Bank, A., On the road to gene therapy for beta-thalassemia and sickle cell anemia (2008) Pediatr Hematol Oncol, 25, pp. 1-4 Shen, T.J., Rogers, H., Yu, X., Lin, F., Noguchi, C.T., Ho, C., Modification of globin gene expression by RNA targeting strategies (2007) Exp Hematol, 35, pp. 1209-1218 Chang, J.C., Ye, L., Kan, Y.W., Correction of the sickle cell mutation in embryonic stem cells (2006) Proc Natl Acad Sci U S A, 103, pp. 1036-1040 Wu, L.C., Sun, C.W., Ryan, T.M., Pawlik, K.M., Ren, J., Townes, T.M., Correction of sickle cell disease by homologous recombination in embryonic stem cells (2006) Blood, 108, pp. 1183-1188 Birgens, H., Ljung, R., The thalassaemia syndromes (2007) Scand J Clin Lab Invest, 67, pp. 11-25 Araújo, A.S., Silva, W.A., Leão, S.A., Bandeira, F.C., Petrou, M., Modell, B., A different molecular pattern of beta-thalassemia mutations in northeast (2003) Brazil. Hemoglobin, 27, pp. 211-217 Taher, A., Isma'eel, H., Cappellini, M.D., Thalassemia intermedia: Revisited (2006) Blood Cells Mol Dis, 37, pp. 12-20 Rund, D., Rachmilewitz, E., Beta-thalassemia (2005) N Engl J Med, 353, pp. 1135-1146 Kuypers, F.A., de Jong, K., The role of phosphatidylserine in recognition and removal of erythrocytes (2004) Cell Mol Biol (Noisy-le-grand), 50, pp. 147-158 Datta, P., Basu, S., Chakravarty, S.B., Chakravarty, A., Banerjee, D., Chandra, S., Enhanced oxidative cross-linking of hemoglobin E with spectrin and loss of erythrocyte membrane asymmetry in hemoglobin E beta-thalassemia (2006) Blood Cells Mol Dis, 37, pp. 77-81 De Franceschi, L., Ronzoni, L., Cappellini, M.D., Cimmino, F., Siciliano, A., Alper, S.L., K-CL co-transport plays an important role in normal and beta thalassemic erythropoiesis (2007) Haematologica, 92, pp. 1319-1326 Ayi, K., Turrini, F., Piga, A., Arese, P., Enhanced phagocytosis of ring-parasitized mutant erythrocytes: A common mechanism that may explain protection against falciparum malaria in sickle trait and beta-thalassemia trait (2004) Blood, 104, pp. 3364-3371 Weiss, M.J., Zhou, S., Feng, L., Gell, D.A., Mackay, J.P., Shi, Y., Role of alpha-hemoglobin-stabilizing protein in normal erythropoiesis and beta-thalassemia (2005) Ann N Y Acad Sci, 1054, pp. 103-117 Toumba, M., Sergis, A., Kanaris, C., Skordis, N., Endocrine complications in patients with Thalassaemia Major (2007) Pediatr Endocrinol Rev, 5, pp. 642-648 Aessopos, A., Berdoukas, V., Tsironi, M., The heart in transfusion dependent homozygous thalassaemia today - prediction, prevention and management (2008) Eur J Haematol, 80, pp. 93-106 Weizer-Stern, O., Adamsky, K., Amariglio, N., Levin, C., Koren, A., Breuer, W., Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell-line HepG2 induced by thalassaemic sera (2006) Br J Haematol, 135, pp. 129-138 Tanno, T., Bhanu, N.V., Oneal, P.A., Goh, S.H., Staker, P., Lee, Y.T., High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin (2007) Nat Med, 13, pp. 1096-1101 Cohen, A.R., Galanello, R., Pennell, D.J., Cunningham, M.J., Vichinsky, E., (2004) Thalassemia, pp. 14-34. , Hematology Am Soc Hematol Educ Program Ataga, K.I., Cappellini, M.D., Rachmilewitz, E.A., Beta-thalassaemia and sickle cell anaemia as paradigms of hypercoagulability (2007) Br J Haematol, 139, pp. 3-13 Panigrahi, I., Agarwal, S., Thromboembolic complications in beta-thalassemia: Beyond the horizon (2007) Thromb Res, 120, pp. 783-789 Amer, J., Fibach, E., N-acetylcysteine amide, a novel cell-permeating thiol, restores cellular glutathione and protects human red blood cells from oxidative stress (2005) Free Radic Biol Med, 38, pp. 136-145 Pattanapanyasat, K., Gonwong, S., Chaichompoo, P., Noulsri, E., Lerdwana, S., Sukapirom, K., Activated platelet-derived microparticles in thalassaemia (2007) Br J Haematol, 136, pp. 462-471 Weinstein, B.I., Erramouspe, B., Albuquerque, D.M., Oliveira, D.M., Kimura, E.M., Costa, F.F., Hb Florida: A novel elongated C-terminal beta-globin variant causing dominant beta-thalassemia phenotype (2006) Am J Hematol, 81, pp. 358-360 Singh, S.P., Gupta, S., Molecular pathogenesis and clinical variability of homozygous beta 0-thalassemia in populations of Jammu region of J&K state (India) (2006) Hematology, 11, pp. 271-275 Kimura, E.M., Grignoli, C.R., Pinheiro, V.R., Costa, F.F., Sonati, M.F., Thalassemia intermedia as a result of heterozygosis for beta 0-thalassemia and alpha alpha alpha anti-3,7 genotype in a Brazilian patient (2003) Braz J Med Biol Res, 36, pp. 699-701 Bailey, L., Kuroyanagi, Y., Franco-Penteado, C.F., Conran, N., Costa, F.F., Ausenda, S., Expression of the gamma-globin gene is sustained by the cAMP-dependent pathway in beta-thalassaemia (2007) Br J Haematol, 138, pp. 382-395 dos Santos, C.O., Costa, F.F., AHSP and beta-thalassemia: A possible genetic modifier (2005) Hematology, 10, pp. 157-161 dos Santos, C.O., Zhou, S., Secolin, R., Wang, X., Cunha, A.F., Higgs, D.R., Population analysis of the alpha hemoglobin stabilizing protein (AHSP) gene identifies sequence variants that alter expression and function (2008) Am J Hematol, 83, pp. 103-108 Franchini, M., Veneri, D., Iron-chelation therapy: An update (2004) Hematol J, 5, pp. 287-292 Pootrakul, P., Sirankapracha, P., Sankote, J., Kachintorn, U., Maungsub, W., Sriphen, K., Clinical trial of deferiprone iron chelation therapy in beta-thalassaemia/haemoglobin E patients in Thailand (2003) Br J Haematol, 122, pp. 305-310 Tsironi, M., Deftereos, S., Andriopoulos, P., Farmakis, D., Meletis, J., Aessopos, A., Reversal of heart failure in thalassemia major by combined chelation therapy: A case report (2005) Eur J Haematol, 74, pp. 84-85 Neufeld, E.J., Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: New data, new questions (2006) Blood, 107, pp. 3436-3441 Choudhry, V.P., Naithani, R., Current status of iron overload and chelation with deferasirox (2007) Indian J Pediatr, 74, pp. 759-764 Yang, L.P., Keam, S.J., Keating, G.M., Deferasirox: A review of its use in the management of transfusional chronic iron overload (2007) Drugs, 67, pp. 2211-2230 Rivera, S., Nemeth, E., Gabayan, V., Lopez, M.A., Farshidi, D., Ganz, T., Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs (2005) Blood, 106, pp. 2196-2199 Higgs, D.R., (2004) Gene regulation in hematopoiesis: New lessons from thalassemia, pp. 1-13. , Hematology Am Soc Hematol Educ Program Weatherall, D.J., Thalassaemia: The long road from bedside to genome (2004) Nat Rev Genet, 5, pp. 625-631 Quek, L., Thein, S.L., Molecular therapies in beta-thalassaemia (2007) Br J Haematol, 136, pp. 353-365 Dissayabutra, T., Tosukhowong, P., Seksan, P., The benefits of vitamin C and vitamin E in children with beta-thalassemia with high oxidative stress (2005) J Med Assoc Thai, 88 (SUPPL. 4), pp. S317-S321 Tesoriere, L., Allegra, M., Butera, D., Gentile, C., Livrea, M.A., Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells (2006) Free Radic Res, 40, pp. 753-761 Ghavamzadeh, A., Iravani, M., Ashouri, A., Mousavi, S.A., Mahdavi, N., Shamshiri, A., Peripheral blood versus bone marrow as a source of hematopoietic stem cells for allogeneic transplantation in children with class I and II beta thalassemia major (2008) Biol Blood Marrow Transplant, 14, pp. 301-308 Sadelain, M., Recent advances in globin gene transfer for the treatment of beta-thalassemia and sickle cell anemia (2006) Curr Opin Hematol, 13, pp. 142-148 Xie, S.Y., Ren, Z.R., Zhang, J.Z., Guo, X.B., Wang, Q.X., Wang, S., Restoration of the balanced alpha/beta-globin gene expression in beta654-thalassemia mice using combined RNAi and antisense RNA approach (2007) Hum Mol Genet, 16, pp. 2616-2625 Moi, P., Sadelain, M., Towards the genetic treatment of beta-thalassemia: New disease models, new vectors, new cells (2008) Haematologica, 93, pp. 325-330