BCL11A Down-Regulation Induces γ-Globin in Human ß-Thalassemia Major Erythroid Cells.

ABSTRACT

Fetal hemoglobin (Hb F, α2γ2) is a potent genetic modifier of the severity of ß-thalassemia (ß-thal) and sickle cell anemia. Differences in the levels of HbF that persist into adulthood affect the severity of sickle cell disease and the ß-thal syndromes. B-cell lymphoma 11 A (BCL11A) is a potent silencer of HbF. Here, we reactivated γ-globin expression by down-regulating BCL11A to alleviate anemia in the ß-thal major (ß-TM) patients. BCL11A were down-regulated by lentiviral RNAi (RNA interference) in the K562 cell line and an in vitro culture model of human erythropoiesis in which erythroblasts are derived from the normal donor mononuclear cells (MNC) or ß-TM MNC. The expression of γ-globin were analyzed by qPCR (quantitative real-time polymerase chain reaction) and Western blot techniques. Our data showed that down-regulation of BCL11A induces γ-globin production in the K562 cell line and human erythrocytes from normal donors and ß-TM donors, without altering erythroid maturation. This is the first report on γ-globin induction by down-regulation of BCL11A in human erythroblasts derived from ß-TM.