alexa Hydroxyurea therapy requires HbF induction for clinical benefit in a sickle cell mouse model.
Chemical Engineering

Chemical Engineering

Journal of Chromatography & Separation Techniques

Author(s): Lebensburger JD, Pestina TI, Ware RE, Boyd KL, Persons DA

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Abstract Hydroxyurea has proven clinical efficacy in patients with sickle cell disease. Potential mechanisms for the beneficial effects include fetal hemoglobin induction and the reduction of cell adhesive properties, inflammation and hypercoagulability. Using a murine model of sickle cell disease in which fetal hemoglobin induction does not occur, we evaluated whether hydroxyurea administration would still yield improvements in hematologic parameters and reduce end-organ damage. Animals given a maximally tolerated dose of hydroxyurea that resulted in significant reductions in the neutrophil and platelet counts showed no improvement in hemolytic anemia and end-organ damage compared to control mice. In contrast, animals having high levels of fetal hemoglobin due to gene transfer with a gamma-globin lentiviral vector showed correction of anemia and organ damage. These data suggest that induction of fetal hemoglobin by hydroxyurea is an essential mechanism for its clinical benefits.
This article was published in Haematologica and referenced in Journal of Chromatography & Separation Techniques

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