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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

5-azacytidine selectively increases gamma-globin synthesis in a patient with beta+ thalassemia.

5-Azacytidine is a cytidine analogue that is capable of activating repressed genes in tissue-culture cells and has been shown to increase hemoglobin-F production in anemic baboons. This drug was administered to a patient with severe beta-thalassemia in an attempt to stimulate hemoglobin-F production. After seven days of 5-azacytidine treatment, gamma-globin synthesis increased approximately sevenfold, temporarily normalizing the patient's unbalanced globin synthesis. Erythropoiesis became more effective, leading to a temporary increase in the absolute reticulocyte count (from 5000 to 22,000 per cubic millimeter) and in hemoglobin concentration (from 8.0 to 10.8 g per deciliter). Hypomethylation of bone-marrow DNA near both the gamma-globin and epsilon-globin genes was directly demonstrated. At the time of peak drug effect, about 7000 gamma-globin messenger RNA molecules were present per erythroid bone-marrow cell, in contrast to 10 to 15 epsilon-globin messenger RNA molecules per cell. 5-Azacytidine selectivity increases gamma-globin synthesis and therefore provides a new approach to the treatment of severe beta-thalassemia. Further studies will be required to evaluate the efficacy, risks, and long-term toxicity of 5-azacytidine (or related compounds) before this approach can be used as a therapy for patients with disorders of hemoglobin synthesis.[1]


  1. 5-azacytidine selectively increases gamma-globin synthesis in a patient with beta+ thalassemia. Ley, T.J., DeSimone, J., Anagnou, N.P., Keller, G.H., Humphries, R.K., Turner, P.H., Young, N.S., Keller, P., Nienhuis, A.W. N. Engl. J. Med. (1982) [Pubmed]
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