الفهرس 
Impact of CYP3A4-(A290G) and CYP2B6 (G516T) polymorphisms on predisposition and prognosis of acute myeloid leukemia
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Abstract
Background: Several genetic single nucleotide polymorphisms have been determined as possible risk factors for the development of leukemia. CYP3A4 and CYP2B6 are abundant cytochrome P450 enzymes in the human liver. CYP3A4-A-290G and CYP2B6-G516T polymorphisms appear to influence the enzymatic expression and activity in drug metabolism and carcinogen inactivation and have been implicated in AML development. Aims: the study aimed to evaluate the impact of CYP3A4-A-290G and CYP2B6-G516T polymorphisms on the predisposition and prognosis of AML. Methodology: the study included 50 newly diagnosed AML cases and 50 age and sex comparable healthy controls. Detection of CYP3A4-A-290G and CYP2B6-G516T polymorphisms was done by molecular PCR/ RFLP. Results: the main findings were increased frequency of mutant CYP2B6 (homozygous and heterozygous) and CYP3A4 (homozygous and heterozygous) genotypes in AML cases compared to control subjects, increased combined gene mutations in AML patient group compared to control subjects. (43.7% vs 5.0%, p=0.003). There was no statistically significant difference between any of the enzyme polymorphisms and early response to treatment. CYP3A4 mutation was significantly associated with worse overall survival. Significant association was found between both CYP3A4-A-290G and CYP2B6-G516T polymorphisms and development of AML (p-values were 0.006 and 0.017 respectively). Conclusion: these findings suggest a pathogenetic role of these gene polymorphisms in AML and a possible bad prognostic impact of CYP3A4-A-290G polymorphism on disease course