Pharmacogenomic Reactivation of Foetal Haemoglobin
Pharmacologically mediated regulation of the expression of the human gamma
(γ) globin genes could be a potential therapeutic approach for haematological
disorders particularly beta (β) thalassaemia and sickle cell disease (SCD). It is a
well-documented fact that an increase of foetal haemoglobin (Hb F) leads to a
considerable improvement of the clinical status of the patients affected by these
haemoglobinopathies. Reactivating the γ-globin gene would greatly ameliorate
the symptoms of β-haemoglobinopathies. Various studies have shown that three
important genes; the v-myb myeloblastosis viral oncogene homolog (MYB), Bcell lymphoma/leukemia 11A (BCL11A) gene and Erythroid Krüppel-Like Factor
(KLF1) gene have an impact on the regulation of Hb F. In this study erythroid
progenitor cells are cultured from patients with KLF1 mutations, β-thalassaemia
and normal healthy adults as controls. The cells are subjected to 3 types of
compounds, hydroxyurea, thalidomide and 5’azacytidine and determine which
combination of drug to patient cells works optimally to augment Hb F.
References
Borg, J., et al (2011) Erythroid phenotypes associated with KLF1 mutations.
Haematologica 96(5):635-638.
Borg, J., et al., (2010) Haploinsufficiency for the Erythroid Transcription Factor
KLF1 Causes Hereditary Persistence of Foetal Haemoglobin. Nature Genetics. 42,
801–805.