AS3MT Polymorphisms, Arsenic Metabolism, and the Hematological and Biochemical Values in APL Patients Treated with Arsenic Trioxide

Abstract

Although arsenic has shown remarkable therapeutic efficacy in patients with acute promyelocytic leukemia (APL), its side effects are rarely reported. In this article, the associations among urinary arsenic profiles, hematological and biochemical values, and 3 AS3MT genotypes (rs3740392, rs3740390, and rs11191439) were evaluated in 50 APL patients treated with arsenic trioxide (As2O3). Results revealed the levels of serum enzymes (ALT, AST, and GGT), GLU and the count of WBC and NEUT#, which were markers of hepatic damage, diabetes and leukocytosis, respectively, were increased significantly 10 days after the administration of As2O3. The percentages of dimethylated arsenic (DMA) and the secondary methylation index (SMI, DMA/MMA) were negatively associated with the levels of ALT and AST. Patients with the AS3MT rs3740390 TC or TT genotype, compared with rs3740390 CC genotype, had significantly higher levels of DMA%, SMI and significantly lower levels of ALT and AST. Furthermore, the frequency for the heterozygous variant of rs11191439 was absolute low (N = 1). For rs3740392, no statistical differences were noted in urinary arsenic profiles and hematological and biochemical values in individuals with different genotypes. These results indicate that inherent genetic information of the AS3MT rs3740390 genotypes is a novel predicted or evaluated target for As2O3-induced side effects and therapeutic efficacy for the treatment of APL.