DNA hypomethylation therapy for hemoglobin disorders: molecular mechanisms and clinical applications

Blood Reviews
Hassana Fathallah, George F Atweh

Abstract

Reactivation of fetal hemoglobin (HbF) expression is an important therapeutic option in patients with hemoglobin disorders. In sickle cell disease (SCD), an increase in HbF would interfere with the polymerization of sickle hemoglobin while in beta-thalassemia, an increase in gamma-globin chain synthesis would decrease non-alpha:alpha chain imbalance. Hydroxyurea, an inducer of HbF, is the only currently approved agent for the treatment of patients with moderate and/or severe SCD. However, about one third of patients with SCD do not respond to HU, and in beta-thalassemia, the clinical response is unimpressive. The last decade has seen a renewed interest in the use of inhibitors of DNA methylation in the treatment of patients with hemoglobin disorders. In this review, we discuss the role of DNA methylation in gamma-globin gene regulation, describe clinical trials with agents that hypomethylate DNA and speculate about the future role of DNA hypomethylation therapy in patients with SCD and beta-thalassemia.

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Citations

Oct 29, 2008·Evidence-based Complementary and Alternative Medicine : ECAM·Nicoletta BianchiRoberto Gambari
Dec 17, 2009·Hemoglobin·Amal El-BeshlawyMona El Ghamrawy
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Nov 28, 2008·British Journal of Haematology·Sara Trompeter, Irene Roberts
Jul 5, 2015·Blood Cells, Molecules & Diseases·Dario CostaClaudio Napoli
Sep 4, 2014·Asian Pacific Journal of Tropical Biomedicine·Abbas NajjariAli Asghar Ahmadi
Jul 25, 2017·American Journal of Hematology·Alawi H HabaraMartin H Steinberg
Feb 13, 2008·American Journal of Hematology·Geoffrey T GibneyDavid H K Chui

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