Anemia Research Today is a free monthly online journal that collates and summarizes the latest research about Anemia, including details on symptoms, diagnosis, diet, treatment, causes. | ||||||||
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Expression of the gamma-globin gene is sustained by the cAMP-dependent pathway in beta-thalassaemia.Bailey L, Kuroyanagi Y, Franco-Penteado CF, Conran N, Costa FF, Ausenda S, Cappellini MD, Ikuta T Department of Medicine, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA, USA. The present study found that the cyclic adenosine monophosphate (cAMP)-dependent pathway efficiently induced gamma-globin expression in adult erythroblasts, and this pathway plays a role in gamma-globin gene (HBG) expression in beta-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 beta-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 phosphorylation levels correlated with HBG mRNA levels of the patients. Other signalling molecules, such as mitogen-activated protein kinases and signal transducers and activators of transcription proteins, were phosphorylated at variable levels and showed no correlations with the HBG mRNA levels. Plasma levels of cytokines, such as erythropoietin, stem cell factor and transforming growth factor-beta were increased in patients, and these cytokines induced both HBG mRNA expression and CREB phosphorylation. These results demonstrate that the cAMP-dependent pathway, the activity of which is augmented by multiple cytokines, plays a role in regulating HBG expression in beta-thalassaemia. Published 6 July 2007 in Br J Haematol, 138(3): 382-95.
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