Authors:
Jian Xu, Cong Peng, Vijay G. Sankaran, Zhen Shao, Erica B. Esrick, Bryan G. Chong, Gregory C. Ippolito, Yuko Fujiwara, Benjamin L. Ebert, Philip W. Tucker, & Stuart H. Orkin
Summary:
Persistence of human fetal hemoglobin (HbF, α2γ2) in adults lessens the severity of sickle cell disease (SCD) and the β-thalassemias. Here, we show that the repressor BCL11A is required in vivo for silencing of γ-globin expression in adult animals, yet dispensable for red cell production. BCL11A serves as a barrier to HbF reactivation by known HbF inducing agents. In a proof-of-principle test of BCL11A as a potential therapeutic target, we demonstrate that inactivation of BCL11A in SCD transgenic mice corrects the hematologic and pathologic defects associated with SCD through high-level pancellular HbF induction. Thus, interference with HbF silencing by manipulation of a single target protein is sufficient to reverse SCD.
Source:
Science; Vol. 334, No. 6058, 993-996 (11/18/11)