title: The switch from fetal to adult hemoglobin.
abstract: The fetal-to-adult hemoglobin switch and silencing of fetal hemoglobin (HbF) have been areas of long-standing interest among hematologists, given the fact that clinical induction of HbF production holds tremendous promise to ameliorate the clinical symptoms of sickle cell disease (SCD) and β-thalassemia. In this article, we discuss historic attempts to induce HbF that have resulted in some therapeutic approaches to manage SCD and β-thalassemia. We then go on to discuss how more recent molecular studies that have identified regulators, including BCL11A, MYB, and KLF1, hold great promise to develop targeted and more effective approaches for HbF induction. We go on to discuss strategies by which such approaches may be developed. Older studies in this field can provide important lessons for future studies aimed at developing more effective strategies for HbF induction, and we therefore chronologically cover the work accomplished as this field has evolved over the course of the past four decades.
authors.affiliation: Division of Hematology/Oncology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA. sankaran@broadinstitute.org
authors.forename: Vijay G
authors.initials: VG
authors.lastname: Sankaran
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000628:therapy; D002352:Carrier Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins; D005319:Fetal Hemoglobin / Q000235:genetics* / Q000378:metabolism; D006441:Hemoglobin A / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D058990:Molecular Targeted Therapy / Q000379:methods; D009687:Nuclear Proteins / Q000235:genetics*; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors; D015533:Transcriptional Activation; D017086:beta-Thalassemia / Q000628:therapy
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; C491719:MYBBP1A protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C080774:erythroid Kruppel-like factor; D006441:Hemoglobin A; D005319:Fetal Hemoglobin