title: Targeted fetal hemoglobin induction for treatment of beta hemoglobinopathies.
abstract: Fetal globin (gamma globin; HBG) is normally expressed during fetal life and prevents the clinical manifestations of beta hemoglobinopathies before birth. HBG genes are normally integrated in hematopoietic stem cells in all humans, and are at least partially amenable to reactivation. Inducing expression of fetal globin (HBG) gene expression to 60% to 70% of alpha globin synthesis produces a β-thalassemia trait phenotype, and reduces anemia. Tailoring combinations of therapeutics to patient subsets characterized for quantitative trait loci which modulate basal fetal hemoglobin and erythroid cell survival should provide effective amelioration of clinical symptoms in β-thalassemia and sickle cell disease.
authors.affiliation: Hemoglobinopathy-Thalassemia Research Unit, Cancer Center, Department of Medicine, Pediatrics, Pharmacology and Experimental Therapeutics, Boston University School of Medicine, 72 East Concord Street, L-909, Boston, MA 02118, USA. Electronic address: sperrine@bu.edu.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Perrine
authors.affiliation: Department of Pediatrics and Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Betty S
authors.initials: BS
authors.lastname: Pace
authors.affiliation: Cancer Center, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Douglas V
authors.initials: DV
authors.lastname: Faller
mesh_terms: D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000235:genetics; D000818:Animals; D002087:Butyrates / Q000494:pharmacology / Q000627:therapeutic use; D005319:Fetal Hemoglobin / Q000235:genetics*; D006453:Hemoglobinopathies / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics*; D055542:alpha-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000188:drug therapy / Q000235:genetics
chemical_list: D002087:Butyrates; D055542:alpha-Globins; D005319:Fetal Hemoglobin
keywords: Beta-thalassemia; Fetal hemoglobin; Genetic modifiers; Sickle cell disease; Stress signaling