Therapeutic Potential of BCL11A Deletion for Patients With Beta Thalassemia

Updated: Dec 3, 2019

Beta-thalassemia is a haemoglobinopathy, characterised by mutations in the HBB gene on chromosome 11 which encode beta globin chains. This results in limited or no production of beta globin chains in HbA, and subsequently limits HbA production which disrupts normal erythrocyte function.

Patients suffer from a range of symptoms such as: spleen enlargement, anaemia, gallstones, iron overload or may even be clinically asymptomatic depending on the disease severity. If left untreated, beta thalassemia can progress on to heart failure and eventually death. Currently, the treatment options are limited to regular blood transfusions which can cause complications with iron overload. Therefore, there is a requirement of novel treatment options.

Now scientists may be able to provide insight into a novel treatment for Beta thalassemia. An article was published in the European Journal of Pharmacology, in which scientists used specific CRISPR-Cas9 gene editing to delete the BCL11A gene in three different human blood cell lines (KU-812, KG-1, and K562 ). BCL11A also known as BAF chromatin remodeling complex subunit BCL11A could be involved in neural development, haematopoesis, leukemogenesis and even more importantly, fetal haemoglobin production.

Anyway, in this study, the deletion of BCL11A erythroid enhancer caused a strong induction of gamma haemoglobin expression levels in K562 cells (but not the other two cell lines, which were poor models for this study). Thereby, deletion of BCL11A erythroid enhancer region may allow fetal haemoglobin reactivation, which may diminish Beta thalassemia. This study may pave the way for further research into HbF reactivation pathways as an alternative treatment for Beta thalassemia.