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The evidence that 5-azacytidine stimulates the production of Hb F and F cells in baboon and man is reviewed. The mechanism of this effect is not entirely clear, but 5-azacytidine produces hypomethylation of the gamma gene at certain sites, and gene expression and DNA hypomethylation are related phenomena in many other systems. Other mechanisms have been postulated by other investigators. The therapeutic significance of increased Hb F levels in homozygous beta thalassemia and sickle cell anemia is exemplified. The potential risk of carcinogenicity has delayed more extensive clinical trials.
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Heller et al. (1984) studied this question.
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