Genetic and epigenetic studies for hbf induction in patients with beta thalassemia major

Our aim is to reveal relationship between genetic variations of KLF1 and BCL11A genes which are implied on HbF induction pathways, and modifying properties of epigenetic mechanisms of resveratrol and sodium butyrate on both K562 cells and primary erythroid cells in patiens with beta thalassemia major. RNA profiles of globin genes, p38, ERK1/2 and NRF2 signalling pathways were evaluated in both K562 cells and primary erythroid cells in 30 well-characterized BTM patients in which were induced with resveratrol and/or sodium butyrate. Among the factors which regulates the amount of HbF; KLF1 whole gene, BCL11A rs11886868 variation and XmnI polymorphisms were investigated by using both RFLP and Sanger Sequencing. Resveratrol and sodium butyrate caused dose-dependent hemoglobinization pattern in K562 cells. No synergistic effect was found between these two agents. Apoptotic effect was observed at high dose resveratrol in K562 cells. The potential of gamma globin induction of both resveratrol and sodium butyrate were elucidated. NRF2, ERK1/2 and p38 activation were screened in K562 cells while there was activation of p38 and inactivation of ERK1/2 pathways in primary erythroid cells of patients. BCL11A rs11886868, XmnI polymorphisms and KLF1 variations were found to be compatible with the literature.Guidance on selection of pharmacological molecules in HbF induction studies, individual genetic and epigenetic factors should be taken account in patients with beta thalassemia major.