5-Azacytidine Selectively Increases γ-Globin Synthesis in a Patient with β+Thalassemia
- 9 December 1982
- journal article
- case report
- Published by Massachusetts Medical Society in The New England Journal of Medicine
- Vol. 307 (24), 1469-1475
- https://doi.org/10.1056/nejm198212093072401
Abstract
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 β-thalassemia in an attempt to stimulate hemoglobin-F production. After seven days of 5-azacytidine treatment, γ-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 γ-globin and ε-globin genes was directly demonstrated. At the time of peak drug effect, about 7000 γ-globin messenger RNA molecules were present per erythroid bone-marrow cell, in contrast to 10 to 15 ε-globin messenger RNA molecules per cell. 5-Azacytidine selectively increases γ-globin synthesis and therefore provides a new approach to the treatment of severe β-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. (N Engl J Med. 1982; 307:1469–75.)Keywords
This publication has 28 references indexed in Scilit:
- Unusual methylation pattern of the α2(I) collagen geneCell, 1982
- 5-Azacytidine-Induced Reactivation of a Herpes Simplex Thymidine Kinase GeneScience, 1982
- Methylation and gene controlNature, 1982
- Genetic Relationship between Fetal Hb Levels in Normal and Erythropoietically Stressed BaboonsBritish Journal of Haematology, 1981
- Electrophoretic separation of human embryonic globin demonstrates “α-thalassemia” in human leukemia cell line K562Biochemical and Biophysical Research Communications, 1980
- DNA methylation in the human γδβ-globin locus in erythroid and nonerythroid tissuesCell, 1980
- Magnitude of the fetal hemoglobin response to acute hemolytic anemia in baboons is controlled by genetic factors.JCI Insight, 1980
- K562 human leukaemic cells synthesise embryonic haemoglobin in response to haeminNature, 1979
- Detection of specific sequences among DNA fragments separated by gel electrophoresisJournal of Molecular Biology, 1975
- Hemoglobin Messenger RNA from Human Bone Marrow ISOLATION AND TRANSLATION IN HOMOZYGOUS AND HETEROZYGOUS β-THALASSEMIAJCI Insight, 1973