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

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 associate...

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Autores principales: Eridani, Sandro, Mosca, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262355/
https://www.ncbi.nlm.nih.gov/pubmed/22287860
http://dx.doi.org/10.2147/JBM.S14942
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author Eridani, Sandro
Mosca, Andrea
author_facet Eridani, Sandro
Mosca, Andrea
author_sort Eridani, Sandro
collection PubMed
description 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.
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spelling pubmed-32623552012-01-27 Fetal hemoglobin reactivation and cell engineering in the treatment of sickle cell anemia Eridani, Sandro Mosca, Andrea J Blood Med Review 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. Dove Medical Press 2011-02-28 /pmc/articles/PMC3262355/ /pubmed/22287860 http://dx.doi.org/10.2147/JBM.S14942 Text en © 2011 Eridani and Mosca, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Review
Eridani, Sandro
Mosca, Andrea
Fetal hemoglobin reactivation and cell engineering in the treatment of sickle cell anemia
title Fetal hemoglobin reactivation and cell engineering in the treatment of sickle cell anemia
title_full Fetal hemoglobin reactivation and cell engineering in the treatment of sickle cell anemia
title_fullStr Fetal hemoglobin reactivation and cell engineering in the treatment of sickle cell anemia
title_full_unstemmed Fetal hemoglobin reactivation and cell engineering in the treatment of sickle cell anemia
title_short Fetal hemoglobin reactivation and cell engineering in the treatment of sickle cell anemia
title_sort fetal hemoglobin reactivation and cell engineering in the treatment of sickle cell anemia
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262355/
https://www.ncbi.nlm.nih.gov/pubmed/22287860
http://dx.doi.org/10.2147/JBM.S14942
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