Micro-RNA Biogenesis Genes (AGO1 and GEMIN4) Single Nucleotide Variants of Bad Prognosis and Poor Therapeutic Response in Egyptian Chronic Myeloid Leukemia Patients: Case–control Study

Abstract

BACKGROUND: Chronic myeloid leukemia (CML) is one of the most common hematological tumors. Gene candidate studies cleared the association of single genetic variants (SNVs) to the risk and progression in CML. MicroRNA biogenesis genes disruption contributes a fundamental role in carcinogenesis. AIM: We aimed to determine the association between rs636832 and rs2740348 SNVs of AGO1 gene and GEMIN4 gene, respectively, and the risk and prognosis in CML Egyptian patients with 5 years survival estimation. METHODS: The study was conducted on 110 newly diagnosed CML patients and 110 age and sex healthy matched controls. Real-time polymerase chain reaction utilizing TaqMan probes was operated to demonstrate genetic modalities of rs636832 and rs2740348. RESULTS: No significance difference was observed between the cases and controls regarding the genotypic and allelic frequencies for both variants. On the other hand, the rs636832 GG genotype was more evident at a younger age of diagnosis and associated with the poor grades of the Sokal and Eutos scores. As well, rs2740348 CC genotype was encountered in high Eutos score levels. Regarding the response therapy, rs636832 GG genotype was overrepresented in the resistance to Imatinib while rs2740348 CC genotype was prevalent in the resistance to both Imatinib and Nilotinib. Overall survival was of no statistical significance for both variants. CONCLUSION: Our study revealed that the major homozygous genotypes of both variants were associated with bad prognostic clinical scores and poor response to therapy but with no role in CML risk.