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Blood, 1 January 2008, Vol. 111, No. 1, pp. 421-429. Prepublished online as a Blood First Edition Paper on October 19, 2007; DOI 10.1182/blood-2007-06-097550. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-06-097550v1 111/1/421    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gabbianelli, M. Articles by Peschle, C. Search for Related Content PubMed PubMed Citation Articles by Gabbianelli, M. Articles by Peschle, C. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Effective erythropoiesis and HbF reactivation induced by kit ligand in β-thalassemia Marco Gabbianelli1, Ornella Morsilli1, Adriana Massa1, Luca Pasquini1, Paolo Cianciulli2, Ugo Testa1, and Cesare Peschle1 1 Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore di Sanità, and 2 Thalassemia Unit, Sant'Eugenio Hospital, Rome, Italy In human β-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 pharmacologic induction of HbF synthesis, clinical trials based on HbF reactivation in β-thalassemia produced inconsistent results. Here, we investigated the in vitro response of β-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 β-thalassemia, addition of KL, alone or combined with dexamethasone (Dex), remarkably stimulated cell proliferation (3-4 logs more than control cultures), while decreasing the percentage of apoptotic and dyserythropoietic cells (<5%). More important, in both thalassemic groups, addition of KL or KL plus Dex induced a marked increase of -globin synthesis, thus reaching HbF levels 3-fold higher than in con-trol cultures (eg, from 27% to 75% or 81%, respectively, in β-thalassemia major). These studies indicate that in β-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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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