Recent studies have also implicated c-MYB in the regulation of expression of fetal hemoglobin which is highly beneficial to the β-hemoglobinopathies (beta thalassemia and sickle cell disease).
Thus we demonstrate how the developmental regulation of a clinically important human trait can be better understood through the genetic and functional study of aneuploidy syndromes and suggest that miR-15a, -16-1, and MYB may be important therapeutic targets to increase HbF levels in patients with sickle cell disease and β-thalassemia.
Genetic variation at 3 principal loci (HBB cluster on chromosome 11p, HBS1L-MYB region on chromosome 6q, and BCL11A on chromosome 2p) have been shown to influence HbF levels and disease severity in β-thalassemia and SCA.
Unfortunately, although recent studies clearly showed a role of SNPs in BCL11A and a HBS1L-MYB region on either clinical expression or fetal hemoglobin levels of beta-hemoglobinopathies such as sickle cell disease and beta-thalassemia, SNPs in BCL11A and the HBS1L-MYB region did not show statistically significant correlations with fetal hemoglobin levels.
The data independently validate for the first time the significance of the HBS1L-MYB intergenic region in regulating HbF expression in a separate ethnic group that has a high prevalence of beta-thalassaemia.