Hydroxyurea is commonly used for Betathalassemia treatment. However its signaling pathway leading to gama-globin induction is not completely understood. Similarities between the signaling pathways of hydroxyurea (HU) and sodium butyrate (SB) suggest involvement of CREB1 in the downstream part of the HU/gama-globin induction signaling pathway. First, both HU and SB lead to G-gama (and not A-gama) induction in erythroid cells. In addition, both HU and SB activate G-gama via p38 MAPK phosphorylation. It has been shown that SB induces G-gama expression through a CREB1/ATF-2 binding site present exclusively in the promoter of G-gama.