Among the DNA-binding agents tested, cisplatin was the most potent inducer of HbF expression, (442☓2%), a level which is comparable to hemin (764☑45%). We show that hydroxyurea and butyrate result in moderate levels of induction (70–80%) but with an additive inductive effect. We compared the EGFP-induction potency of a number of chemotherapeutic agents, including histone deacetylase inhibitors and DNA-binding agents. We show that human erythroleukemic cell lines stably transfected with a Gγ-EGFP β-globin locus construct can maintain a uniform basal level of EGFP expression over long periods of continuous culture and that induction of EGFP expression parallels the induction of the endogenous globin genes. We describe the development of stable cellular genomic reporter assays (GRAs) based on the green fluorescence protein (EGFP) gene under the Gγ-globin promoter in the intact human β-globin locus. However, the drugs currently available have low efficacy and specificity and are associated with high toxicity. Reactivation of fetal hemoglobin (HbF) expression using pharmacological agents represents a potential strategy for the therapy of β-thalassemia, sickle cell disease, HbE and other β-hemoglobinopathies.
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