Abstract:
Chronic myeloid leukemia (CML) is a type of blood cancer that begins in the hematopoietic stem
cell (HSC) compartment. It is characterized by a specific chromosomal aberration known as the
Philadelphia (Ph) chromosome, which arises from a reciprocal translocation between
chromosomes 9 and 22, leading to the union of the BCR and ABL1 genes. While the fusion gene
is a major contributor to CML, several other genes are also implicated in the disease's progression.
Until recently, little research had been conducted to identify single nucleotide polymorphisms
(SNPs) associated with CML. Therefore, this study aims to investigate the influence of missense
variants on the structure and function of the ADGRE2 gene and to identify missense variants
associated with CML and its clinical and pathological characteristics. Missense variants of
ADGRE2 were retrieved from the ENSEMBL genome browser, and the pathogenicity of
deleterious variants was assessed using six different consensus tools. Additionally, various in silico
tools were employed to explore the relationship between damaging SNPs, function, stability, and
structure. Genotype analysis was performed on collected blood samples, revealing that the most
pathogenic SNP among all missense variants was rs765071211 (D67N). Significant differences
were observed between the wild-type and mutant variant (D67N) structures of ADGRE2.
Genotype analysis indicated an association between the variant and CML, as genotypes CT and
TT were found to have significant P-values. Genotype heterozygous CT has been identified as a
risk factor for CML, while TT has a protective role in CML patients. This study suggests that the
ADGRE2 SNP rs765071211 could serve as a potential genetic marker for the diagnosis of CML.
