Estimation of the difference in HbF expression due to loss of the 5' δ-globin BCL11A binding region

Haematologica. 2013 Feb;98(2):305-8. doi: 10.3324/haematol.2012.061994. Epub 2012 Jul 16.

Abstract

BCL11A was the focus of recent studies on its inhibiting effect when bound onto the β-globin cluster in the mechanism of hemoglobin switching and HbF downregulation. We examined a cohort of 10 patients displaying different HbF levels and short deletions within the γβ-δ intergenic region to find a possible correlation with the BCL11A binding site located 5' to the δ-globin gene. Precise characterization of deletions was achieved using a custom DNA-array chip and breakpoint sequencing. The α-globin cluster and major SNP associated with HbF expression were genotyped. Our results show that the loss of the BCL11A binding domain located 5' to the δ-globin gene is correlated with a strong HbF difference (mean+2.7 g/dL, ratio 2.81). This result provides evidence for the use of BCL11A level down-regulation or this domain blockage for new therapies in sickle cell disease and β-thalassemia major patients.

MeSH terms

  • Adolescent
  • Adult
  • Binding Sites
  • Carrier Proteins / metabolism*
  • Child
  • Child, Preschool
  • Female
  • Fetal Hemoglobin / genetics*
  • Fetal Hemoglobin / metabolism
  • Gene Deletion
  • Gene Expression
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Nuclear Proteins / metabolism*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Protein Binding
  • Repressor Proteins
  • Young Adult
  • delta-Globins / genetics*
  • delta-Globins / metabolism*

Substances

  • BCL11A protein, human
  • Carrier Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • delta-Globins
  • Fetal Hemoglobin