Hemoglobin Research and the Origins of Molecular Medicine

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2008 Nov 8

PMID 18988877

Citations 126

Authors

Alan N Schechter

Affiliations

Soon will be listed here.

Abstract

Much of our understanding of human physiology, and of many aspects of pathology, has its antecedents in laboratory and clinical studies of hemoglobin. Over the last century, knowledge of the genetics, functions, and diseases of the hemoglobin proteins has been refined to the molecular level by analyses of their crystallographic structures and by cloning and sequencing of their genes and surrounding DNA. In the last few decades, research has opened up new paradigms for hemoglobin related to processes such as its role in the transport of nitric oxide and the complex developmental control of the alpha-like and beta-like globin gene clusters. It is noteworthy that this recent work has had implications for understanding and treating the prevalent diseases of hemoglobin, especially the use of hydroxyurea to elevate fetal hemoglobin in sickle cell disease. It is likely that current research will also have significant clinical implications, as well as lessons for other aspects of molecular medicine, the origin of which can be largely traced to this research tradition.

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References

Russell J . A post-transcriptional process contributes to efficient gamma-globin gene silencing in definitive erythroid cells. Eur J Haematol. 2007; 79(6):516-25. DOI: 10.1111/j.1600-0609.2007.00970.x. View

Bresnick E, Johnson K, Kim S, Im H . Establishment and regulation of chromatin domains: mechanistic insights from studies of hemoglobin synthesis. Prog Nucleic Acid Res Mol Biol. 2006; 81:435-71. DOI: 10.1016/S0079-6603(06)81011-1. View

Steinberg M . Predicting clinical severity in sickle cell anaemia. Br J Haematol. 2005; 129(4):465-81. DOI: 10.1111/j.1365-2141.2005.05411.x. View

BUNN H, GABBAY K, Gallop P . The glycosylation of hemoglobin: relevance to diabetes mellitus. Science. 1978; 200(4337):21-7. DOI: 10.1126/science.635569. View

Hardison R, Chui D, Riemer C, Giardine B, Lehvaslaiho H, Wajcman H . Databases of human hemoglobin variants and other resources at the globin gene server. Hemoglobin. 2001; 25(2):183-93. DOI: 10.1081/hem-100104027. View

Winslow R . The role of hemoglobin oxygen affinity in oxygen transport at high altitude. Respir Physiol Neurobiol. 2007; 158(2-3):121-7. DOI: 10.1016/j.resp.2007.03.011. View

Weatherall D, Miller L, Baruch D, Marsh K, Doumbo O, Casals-Pascual C . Malaria and the red cell. Hematology Am Soc Hematol Educ Program. 2002; :35-57. DOI: 10.1182/asheducation-2002.1.35. View

Yu B, Raher M, Volpato G, Bloch K, Ichinose F, Zapol W . Inhaled nitric oxide enables artificial blood transfusion without hypertension. Circulation. 2008; 117(15):1982-90. PMC: 2733227. DOI: 10.1161/CIRCULATIONAHA.107.729137. View

Sadelain M . Recent advances in globin gene transfer for the treatment of beta-thalassemia and sickle cell anemia. Curr Opin Hematol. 2006; 13(3):142-8. DOI: 10.1097/01.moh.0000219658.57915.d4. View

10.

Kato G, Gladwin M, Steinberg M . Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Rev. 2006; 21(1):37-47. PMC: 2048670. DOI: 10.1016/j.blre.2006.07.001. View

11.

Thein S . Genetic insights into the clinical diversity of beta thalassaemia. Br J Haematol. 2004; 124(3):264-74. DOI: 10.1046/j.1365-2141.2003.04769.x. View

12.

Clark B, Thein S . Molecular diagnosis of haemoglobin disorders. Clin Lab Haematol. 2004; 26(3):159-76. DOI: 10.1111/j.1365-2257.2004.00607.x. View

13.

Goren A, Simchen G, Fibach E, Szabo P, Tanimoto K, Chakalova L . Fine tuning of globin gene expression by DNA methylation. PLoS One. 2006; 1:e46. PMC: 1762317. DOI: 10.1371/journal.pone.0000046. View

14.

Gaszner M, Felsenfeld G . Insulators: exploiting transcriptional and epigenetic mechanisms. Nat Rev Genet. 2006; 7(9):703-13. DOI: 10.1038/nrg1925. View

15.

Neel J . The Inheritance of Sickle Cell Anemia. Science. 1949; 110(2846):64-6. DOI: 10.1126/science.110.2846.64. View

16.

Letvin N, Linch D, Beardsley G, McIntyre K, Nathan D . Augmentation of fetal-hemoglobin production in anemic monkeys by hydroxyurea. N Engl J Med. 1984; 310(14):869-73. DOI: 10.1056/NEJM198404053101401. View

17.

Miles J, Mitchell J, Chakalova L, Goyenechea B, Osborne C, ONeill L . Intergenic transcription, cell-cycle and the developmentally regulated epigenetic profile of the human beta-globin locus. PLoS One. 2007; 2(7):e630. PMC: 1910613. DOI: 10.1371/journal.pone.0000630. View

18.

Martin D, Fiering S, Groudine M . Regulation of beta-globin gene expression: straightening out the locus. Curr Opin Genet Dev. 1996; 6(4):488-95. DOI: 10.1016/s0959-437x(96)80072-4. View

19.

Taher A, Ismaeel H, Cappellini M . Thalassemia intermedia: revisited. Blood Cells Mol Dis. 2006; 37(1):12-20. DOI: 10.1016/j.bcmd.2006.04.005. View

20.

Hanna J, Wernig M, Markoulaki S, Sun C, Meissner A, Cassady J . Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science. 2007; 318(5858):1920-3. DOI: 10.1126/science.1152092. View