ALL results from an acquired or a genetic injury to the DNA of a single cell in the marrow. The effects of ALL include uncontrolled and exaggerated growth and accumulation of cells called “lymphoblasts” or “leukemic blasts,” which fail to function as normal blood cells.
The presence of the leukemic blasts blocks the production of normal cells. As a result, when ALL is diagnosed, the number of healthy blood cells (red blood cells, white blood cells and platelets) is usually lower than normal.
It has been shown that miRNAs may regulate DNA methylation and control the expression of histone deacetylases and histone methyltransferases for example mirna 502 that regulate SET8 gene by the sequence-specific binding to target mRNA . But the binding affinity may be affected by SNPs residing in miRNA target sites, which may in turn affect the miRNAs’ ability to inhibit the mRNA translation into proteins or lead to degradation of the mRNA .
Indeed, many studies have demonstrated that SNPs at miRNA-binding sites are likely to affect expression of the miRNA target genes and thus may contribute to susceptibility to cancer. Many studies have also shown that SNPs at miRNA-binding sites play a role as novel biomarkers for cancer risk.
The aim of this study was to highlight the association of rs16917496 polymorphism in the miR-502-binding site of SETD8 3′UTR and the risk of childhood ALL.
The current study included forty newly diagnosed patients with ALL, in addition to forty age and sex matched normal children as a control group. All patients were subjected to full history taking, clinical examination, Laboratory investigations. All subjects were genotyped for SET8 rs16917496 C/T polymorphism using PCR- RFLP technique.
The present study demonstrated a lower significant hemoglobin concentration and platelet count in ALL group when compared to control group, and a higher significant total leucocytic count in ALL group when compared to control group(P>0.05).
The present study showed that the most prevalent genotype in control subjects was TT genotype , also T allele has significantly lower frequency in ALL cases when compared to control subjects. So, the TT genotype and T allele in SET8 rs16917496 C/T polymorphism has a protective effect against ALL development.
From this study we concluded that:
- The rs16917496 CT genotype was significantly higher in ALL subjects compared to those carrying either the CC or TT .
- The rs16917496 TT genotype was the most prevalent one in control subjects .
- T allele showed significantly lower frequency in ALL cases when compared to control subjects
- This enable to recognize children at risk of developing ALL by genotyping 3UTR of SETD8 gene, So their own stem cells can be conserved for bone marrow transplantation.
- SNPs at miRNA binding sites represent a promising class of genetic variations worth being deeply investigated as markers of individual susceptibility to ALL.
- Despite accumulating evidence that inherited genetic variation can contribute to a predisposition for pediatric ALL and the suggested role of miRNAs in the development of this disease, as well as the role of miRNA- related polymorphisms in cancer risk, the SNPs in miRNA genes and miRNA-processing genes have not been extensively studied in association with pediatric ALL risk.