Retroviral transfer of a human fetal globin gene carrying the -202 G gamma beta (+)-HPFH mutation into the human erythroleukemia line, KMOE.

The presence of point mutations at position -202 relative to the mRNA Cap site of both human fetal gamma-globin genes is linked with elevated fetal globin levels in adults. The question addressed in this study is whether the -202 mutation affects gamma-globin gene expression in the same manner as the -117 hereditary persistence of fetal hemoglobin (HPFH) A gamma-globin mutation. The -117 mutation was found to cause over-expression and confer inducibility of a retrovirally transferred gamma-globin gene in cytosine arabinoside (araC)-treated KMOE cells in an earlier study. In this study, fetal globin genes driven by either the normal G gamma or -202 HPFH G gamma-globin promoter were retrovirally transferred into human erythroid KMOE cells. The -202 HPFH mutation did not cause over-expression or confer inducibility of the transferred gamma-globin gene in araC-treated KMOE cells. Thus, the -202 HPFH mutation affects gamma-globin gene expression by a different mechanism than the -117 HPFH mutation. Furthermore, this study provides evidence against a general increasing of gamma-globin gene expression as might be expected from the -202 mutation altering binding of a ubiquitous factor such as Sp1.