目的 评估WT1 rs16754多态性对老年急性髓系白血病(AML)患者化疗敏感性和预后的影响.方法 本研究为回顾性分析,收集老年AML患者(≥60岁)的外周血或骨髓样本178例.另外收集65例化疗前AML患者的骨髓样本进行RNA提取,多态性位点的基因型和其他变量的相关性通过Logistic回归模型进行分析.通过Cox模型对其他变量进行校正.结果 WT1基因rs16754位点位于该基因编码区,在研究人群的基因分布频率为:GG型99例(55.62％),GA型67例(37.64％),AA型12例(6.74％),最小等位基因频率为0.26,三种基因型分布频率符合哈迪温伯格平衡(P =0.884).不同基因型患者基线临床资料分布均衡.携带A等位基因的GA/AA型患者和GG型患者的中位总生存期(OS)分别为2.73和1.64年(P=0.003).两种基因型患者的中位无复发生存期(RFS)分别为2.06和1.12年(P=0.032).对OS和RFS构建的多变量Cox模型校正之后发现GA/AA基因型患者较好的OS影响仍然存在(HR =0.51,P=0.013).另外,进一步在65例骨髓标本的表达分析中发现,GG型患者相对于GA/AA基因型的患者,骨髓细胞中WT1 mRNA表达显著较高(P＜0.001).结论 在接受阿糖胞苷为基础化疗的老年AML患者中,WT1基因rs16754位点可能通过影响WT1mRNA的表达从而影响了老年AML患者的预后.%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.
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