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

N Engl J Med. 1982 Dec 9;307(24):1469-75. doi: 10.1056/NEJM198212093072401.


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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Azacitidine / pharmacology*
  • Azacitidine / therapeutic use
  • DNA / metabolism
  • Erythropoiesis / drug effects
  • Gene Expression Regulation / drug effects
  • Globins / biosynthesis*
  • Globins / genetics
  • Hemoglobins / analysis
  • Humans
  • Male
  • Methylation
  • RNA, Messenger / metabolism
  • Stimulation, Chemical
  • Thalassemia / drug therapy
  • Thalassemia / metabolism*


  • Hemoglobins
  • RNA, Messenger
  • Globins
  • DNA
  • Azacitidine