Influence of single nucleotide polymorphism of Wilms tumor 1 gene on the efficacy and clinical prognosis of elderly patients with acute myeloid leukemia

Abstract

Objective To evaluate the influence of single nucleotide polymorphism of Wilms tumor 1(WT1)gene rs16754 on the chemosensitivity and clinical outcomes of elderly patients with acute myeloid leukemia(AML). Methods A total of 178 AML patients aged 60 years and over who received cytarabine-based chemotherapy were enrolled in this retrospective study.The peripheral blood was extracted from 178 AML patients receiving chemotherapy for DNA preparation and study.And bone marrow specimens were collected in 65 AML patients before chemotherapy.The Wilms' Tumor-1(WT1)rs16754 polymorphism was detected by PCR-RFLP method.The association between genotypes and other variables were analyzed by using Logistic regression model.Variables were adjusted by Cox regression analysis. Results The locus of WT1 gene rs16754 is located in coding region of WT1 gene.The genotype frequency and distribution of the studied population were 55.62%(99/178)in GG, 37.64%(67/178)in GA, and 6.74%(12/178)in AA, with minimum allele frequencies of 0.26.The distributions of the three genotypes were in accordance with Hardy-Weinberg Equilibrium(P=0.884). There was no statistical difference in the data distribution of the genotypes on clinical indexes at baseline.Overall survival time(OS)was longer in patients with allele A and genotype GA plus AA[2.73 years(95%CI: 1.03-5.11 years)]than in patients with GG genotype[1.64 years(95%CI: 0.71-4.34), (P=0.003)]. The replase free survival(RFS)was longer in patients with allele A and genotype GA plus AA[2.06 years(95%CI: 0.95-4.87)]than in patients with GG genotype[1.12 years(95%CI: 0.56-4.11), P=0.032)]. Adjusted by using multivariate Cox regression analysis, GA plus AA genotypes still showed a better effect on OS(HR=0.51, P=0.013)than did GG genotypes.In the 65 pretreatment bone marrow specimens, the expression level of WT1 mRNA in bone marrow cells was higher in patients with GG genotype than in patients with GA plus AA genotype(P<0.001). Conclusions Among elderly AML patients treated by cytarabine-based chemotherapy, the WT1 rs16754 may impact the clinical prognosis of AML patients by influencing the mRNA expression of WT1. Key words: Leukemia, myeloid; Polymorphism, single nucleotide; Treatment outcome