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

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.

journal_name

Haematologica

journal_title

Haematologica

authors

Ghedira ES,Lecerf L,Faubert E,Costes B,Moradkhani K,Bachir D,Galactéros F,Pissard S

doi

10.3324/haematol.2012.061994

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

305-8

issue

2

eissn

0390-6078

issn

1592-8721

pii

haematol.2012.061994

journal_volume

98

pub_type

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