Epigenetic Reexpression of Hemoglobin F Using Reversible LSD1 Inhibitors: Potential Therapies for Sickle Cell Disease.

ABSTRACT: Sickle cell disease (SCD) is caused by a single nucleotide polymorphism on chromosome 11 in the β-globin gene. The resulting mutant hemoglobin S (HbS) is a poor oxygen transporter and causes a variety of vascular symptoms and organ failures. At birth, the DRED epigenetic complex forms and silences the γ-globin gene, and fetal hemoglobin (HbF, 2 α-, and 2 γ-subunits) is replaced by adult HbA (α₂β₂) or HbS (α₂β^s ₂) in SCD patients. HbF is a potent inhibitor of HbS polymerization, thus alleviating the symptoms of SCD. The current therapy, hydroxyurea (HU), increases γ-globin and the HbF content in sickle cells but is highly underutilized due to concern for adverse effects and other complications. The DRED complex contains the epigenetic e

SUBMITTER: Holshouser S 

PROVIDER: S-EPMC7315572 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature