Back to Journals » Journal of Blood Medicine » Volume 2

Fetal hemoglobin reactivation and cell engineering in the treatment of sickle cell anemia

Authors Eridani S, Mosca A

Published 28 February 2011 Volume 2011:2 Pages 23—30


Review by Single anonymous peer review

Peer reviewer comments 2

Sandro Eridani, Andrea Mosca
Department of Biomedical Science and Technology, University of Milano, Italy

Abstract: The natural history of severe hemoglobinopathies like sickle cell disease (SCD) is rather variable, depending on the circumstances, but the main influence on such variability is the level of fetal hemoglobin (HbF) in the patient's red cells. It is well known that a significant HbF level is associated with a milder course of disease and fewer complications. Therefore, attempts have been made to reactivate using various means the HbF production, which is normally switched off perinatally. A pharmacological approach has been attempted since the 1980s, ranging from drugs like 5-azacytidine and its derivative, decitabine, to a series of compounds like hydroxyurea and a number of histone deacetylase inhibitors like butyrate, which seem to act as epigenetic modifiers. Many other disparate agents have been tried with mixed results, but hydroxyurea remains the most effective compound so far available. Combinations of different compounds have also been tried with some success. Established treatments like bone marrow or cord blood transplantation are so far the only real cure for a limited number of patients with severe hemoglobinopathies. Improved chemotherapy regimens of milder toxicity than those employed in the past have made it possible recently to obtain a stable, mixed donor-recipient chimerism, with reversal of the SCD phenotype. However, great effort is directed to cell engineering, searching for an effective gene vector by which a desired gene can be transferred into new classes of vectors for autologous hemopoietic stem cells. Recent studies are also aiming at targeted insertion of the therapeutic gene into hemopoietic cells, which can also be “induced” human stem cells, obtained from somatic dedifferentiated cells. Attention in this area must be paid to the possibility of undesired effects, like the emergence of potentially oncogenic cell populations. Finally, an update is presented on improved HbF determination methods, because common international standards are becoming mandatory.

Keywords: sickle cell disease, hemoglobin F, determinants, inducers, cell engineering, induced pluripotent stem cells

Creative Commons License © 2011 The Author(s). This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.