[The role of hydroxyurea in globin gene expression and cell differentiation of human erythroleukemia cell line]

The HEL cells, a human erythroleukemia cell line, express mainly the fetal globin gene and small amount of the embryonic (epsilon) globin gene, but not the adult (beta) globin gene. Hydroxyurea, a small organic compound, has been successfully used to treat sickle cell anemia and beta-thalessaemia. Our data demonstrated that the growth rate of HEL cell proliferation was inhibited by different doses of hydroxyurea (from 50 mumol/L to 200 mumol/L). Using both routine RT-PCR and quantitative PCR analyses, we revealed that the expression of beta-globin gene was sharply activated and alpha-globin gene was almost completely silenced when HEL cells were induced for 3 or 5 days. Meanwhile, gamma-globin gene was expressed with no much difference between induced and uninduced HEL cells. We also demonstrated that the expression of GATA-1 and NF-E 2, which were two of the most important transcription factors in erythrocyte development, was activated about 3 folds in the induced cells. We suggested that the induction of GATA-1 and NF-E 2 expression by hydroxyurea might lead to activation of the adult beta-globin gene through some pathways of signal transduction, therefore, hydroxyurea might play a role to induce HEL cells to terminal differentiation.