Submitted June 22, 2007
Accepted September 21, 2007
Effective erythropoiesis and HbF reactivation induced by kit ligand in 
-thalassemia
Marco Gabbianelli, Ornella Morsilli, Adriana Massa, Luca Pasquini, Paolo Cianciulli, Ugo Testa, and Cesare Peschle*
Dept of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanita, Rome, Italy
Thalassemia Unit, Sant'Eugenio Hospital, Rome, Italy
* Corresponding author; email: cesare.peschle{at}iss.it.
In human 
-thalassemia the imbalance between 
and non- globin chains causes ineffective erythropoiesis, hemolysis and anemia: this condition is effectively treated by an enhanced level of fetal hemoglobin (HbF). In spite of extensive studies on pharmacological induction of HbF synthesis, clinical trials based on HbF reactivation in -thalassemia produced inconsistent results. Here, we investigated the in vitro response of -thalassemic erythroid progenitors to kit ligand (KL) in terms of HbF reactivation, stimulation of effective erythropoiesis and inhibition of apoptosis. In unilineage erythroid cultures of 20 patients with intermedia or major -thalassemia, addition of KL, alone or combined with dexamethasone (Dex), remarkably stimulated cell proliferation (3-4 logs over control cultures), while decreasing the percentage of apoptotic and dyserythropoietic cells (<5%). More important, in both thalassemic groups addition of KL or KL+Dex induced a marked increase of 
-globin synthesis, thus reaching HbF levels three-fold higher than in control cultures (e.g., from 27% to 75% or 81% respectively in -thalassemia major). These studies indicate that in -thalassemia KL, alone or combined with Dex, induces an expansion of effective erythropoiesis and the reactivation of -globin genes up to fetal levels and may hence be considered as a potential therapeutic agent for this disease.
