Abstract
Fetal hemoglobin (HbF) can blunt the pathophysiology, temper the clinical course, and offer prospects for curative therapy of sickle cell disease. This review focuses on (1) HbF quantitative trait loci and the geography of β-globin gene haplotypes, especially those found in the Middle East; (2) how HbF might differentially impact the pathophysiology and many subphenotypes of sickle cell disease; (3) clinical implications of person-to-person variation in the distribution of HbF among HbF-containing erythrocytes; and (4) reactivation of HbF gene expression using both pharmacologic and cell-based therapeutic approaches. A confluence of detailed understanding of the molecular basis of HbF gene expression, coupled with the ability to precisely target by genomic editing most areas of the genome, is producing important preliminary therapeutic results that could provide new options for cell-based therapeutics with curative intent.
© 2020 by The American Society of Hematology.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Anemia, Sickle Cell / blood*
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Anemia, Sickle Cell / complications
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Anemia, Sickle Cell / drug therapy
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Anemia, Sickle Cell / physiopathology
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Fetal Hemoglobin / biosynthesis
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Fetal Hemoglobin / genetics*
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Gene Editing
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Gene Expression Regulation / drug effects
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Gene Knockdown Techniques
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Genetic Therapy
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Genetic Vectors / therapeutic use
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Haplotypes
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Humans
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Hydroxyurea / pharmacology
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Hydroxyurea / therapeutic use
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Lentivirus / genetics
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Microfilament Proteins / genetics
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Polymorphism, Single Nucleotide
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Proto-Oncogene Proteins c-myb / genetics
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Quantitative Trait Loci
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RNA Interference
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RNA, Small Interfering / administration & dosage
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Receptors, Cell Surface / genetics
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Repressor Proteins / antagonists & inhibitors
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Repressor Proteins / genetics
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Stroke / etiology
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beta-Globins / genetics
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gamma-Globins / genetics
Substances
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ANTXR1 protein, human
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BCL11A protein, human
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MYB protein, human
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Microfilament Proteins
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Proto-Oncogene Proteins c-myb
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RNA, Small Interfering
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Receptors, Cell Surface
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Repressor Proteins
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beta-Globins
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gamma-Globins
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Fetal Hemoglobin
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Hydroxyurea