Since the “sickle” shape of the cells is due to a point mutation and the genome of the infected cells can’t be changed we must look into the biochemical pathways that HU affects. Throughout the literature the main theme has been discussing …show more content…
This does, however, bring to fruition a deep dive into the biochemical pathways that HU effects. Pule et al. expanded on the knowledge base surrounding how HU induces the γ-globin expression in cord blood cells. While this does not combat the β6 point mutation, the γ-globin upregulates the amount of HbF that is produced in the body. The use of cord blood, is warranted here because the goal of the research is to study the genes that are regulators of γ-globin. In order to have a better grasp on the increased production the group analyzed the genes that are expressed on miRNA which will code for this upregulation. BCL11A, KLF-1, and MYB all were shown to have an effect; in the same light they are all part of the same pathway therefore the lineage of these regulators is very important in the increase of HbF production. They found that 6 hours after initiation of HU treatment there was a down regulation of BCL11A and at this same time point there was a sevenfold upregulation of γ-globin. They also noticed a down regulation of KLF-1 and MYB whose lowest point came at 12 hours. These genes are intimately linked in a cascade where MYB activates KLF-1 and KLF-1 activates BCL11A, the researchers also claimed BCL11A to be fundamental to the “fetal switch” from γ- to β-globin. Hopefully …show more content…
Genetically, they came to a similar conclusion as Pule in that BCL11A and MYB are large factors in the treatment of sickle cell. However, they also introduced a single nucleotide polymorphism on chromosome 11 that has an upstream effect on the production of the γ-globin gene. While they acknowledged the link between this SNP and the metabolism of arginine to nitric oxide, a vasodilator, and a transcription factor that induces DNA bending, a clear association to HbF was not