Expression of the gamma-globin gene is sustained by the cAMP-dependent pathway in beta-thalassaemia
- L. Bailey
- Y. Kuroyanagi
- C. F. Franco Penteado
- N. Conran
- F. F. Costa
- S. Ausenda
- T. Ikuta
- M.D. Cappellini
DOIAbstract
The present study found that the cyclic adenosine monophosphate (cAMP)-dependent pathway efficiently induced γ-globin expression in adult erythroblasts, and this pathway plays a role in γ-globin gene (HBG) expression in β-thalassaemia. Expression of HBG mRNA increased to about 46% of non-HBA mRNA in adult erythroblasts treated with forskolin, while a cyclic guanosine monophosphate (cGMP) analogue induced HBG mRNA to levels <20% of non-HBA mRNA. In patients with β-thalassaemia intermedia, cAMP levels were elevated in both red blood cells and nucleated erythroblasts but no consistent elevation was found with cGMP levels. The transcription factor cAMP response element binding protein (CREB) was phosphorylated in nucleated erythroblasts and its...
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