β-thalassemias are caused by nearly 300 mutations of the β-globin gene, leading to a low or absent production of adult hemoglobin (HbA). Two major therapeutic approaches have recently been proposed: gene therapy and induction of fetal hemoglobin (HbF) with the objective of achieving clinically relevant levels of Hbs. The objective of this article is to describe the development of therapeutic st...

Differences in the amount of fetal hemoglobin (HbF) that persists into adulthood affect the severity of sickle cell disease and the beta-thalassemia syndromes. Genetic association studies have identified sequence variants in the gene BCL11A that influence HbF levels. Here, we examine BCL11A as a potential regulator of HbF expression. The high-HbF BCL11A genotype is associated with reduced BCL11...

Reactivation of fetal hemoglobin (HbF) holds therapeutic potential for sickle cell disease and β-thalassemias. In human erythroid cells and hematopoietic organs, LIN28B and its targeted let-7 microRNA family, demonstrate regulated expression during the fetal-to-adult developmental transition. To explore the effects of LIN28B in human erythroid cell development, lentiviral transduction was used ...

ONSIDERABLE EVIDENCE IS now available indicating that normal adult hemoglobin (hemoglobin A) is heterogeneous. Sharp and well-defined fractions of hemoglobin A, designated A2 and A3, were obtained by Kunkel (11), who used insoluble potato starch as a supporting medium for electrophoresis. Kunkel also was the first to measure quantitatively the amount of hemoglobin A2 and to correlate increases ...

BACKGROUND Fetal hemoglobin level is a heritable complex trait that strongly correlates swith the clinical severity of sickle cell disease. Only few genetic loci have been identified as robustly associated with fetal hemoglobin in patients with sickle cell disease, primarily adults. The sole approved pharmacologic therapy for this disease is hydroxyurea, with effects largely attributable to ind...

The dominant hemoglobin of the adult hamster was detected in yolk-sac erythroid cells, and its identity was confirmed by peptide mapping and by analysis of relevant peptides. Both the presence and active synthesis of two embryonic hemoglobins presumed to exist only in yolk-sac erythroid cells were detected in neonatal liver and spleen. Thus the time span of expression of both embryonic and adul...

The quantization of glycated isoforms of hemoglobin has been increasingly used in clinical practice in recent years. Glycated hemoglobin is currently considered the most important measurement for long-term control of the glycemic state and it has become a reference tool for the management of diabetes. Glutathionylated hemoglobin is an increasingly clinically relevant covalent adduct of glutathi...

A procedure is described for visualization of cells that had only fetal hemoglobin apnormal and mutant adult hemoglobins in peared as clear ghosts. Analyses of cord human blood smears. After extraction of blood from newborn infants indicate that, blood smears with a concentrated poalthough most erythrocytes contain only Hb tassium phosphate buffer (2.76 M, pH 7.2), F and a few contain only Hb A...

Since KORBER1) discovered in 1865 that human fetal hemoglobin is more resistant to alkali than the adult one, numerous works indicating differences in properties of the fetal and the adult pigment have been published . Biochemically, a considerable dissimilarity is found in their amino acid compositions and primary structures, i. e. amino acid sequences2). Physiologically , it has long been kno...