Sodium butyrate enhances fetal globin gene expression in erythroid progenitors of patients with Hb SS and ß thalassemia

Increasing the expression of the ? globin genes is considered a useful therapeutic approach to the ß globin diseases. Because butyrate and a-amino-n-butyric acid (ABA) augment ? globin expression in normal neonatal and adult erythroid progenitors, we investigated the effects of sodium butyrate and ABA on erythroid progenitors of patients with ß thalassemia and sickle cell anemia who might benefit from such an effect. Both substances increased fetal hemoglobin (Hb F) expression in Bfu-e from 7% to 30% above levels found in control cultures from the same subjects with sickle cell anemia. The fraction of cultured erythroblasts producing Hb F increased more than 20% with sodium butyrate treatment in 70% of cultures. In most cultures, this produced > 20% total Hb F and > 70% F cells, levels which have been considered beneficial in ameliorating clinical symptoms. Alpha: non-alpha (a-non-a) imbalance was decreased by 36% in erythroid progenitors of patients with ß thalassemia cultured in the presence of butyrate compared with control cultures from the same subjects. These data suggest that sodium butyrate may have therapeutic potential for increasing ? globulin expression in the ß globin diseases.