评估DNMT3A基因多态性作为急性髓系白血病患者预后预测指标
Evaluation of DNMT3A genetic polymorphisms as outcome predictors in AML patients.
作者信息
Yuan Xiao-Qing, Zhang Dao-Yu, Yan Han, Yang Yong-Long, Zhu Ke-Wei, Chen Yan-Hong, Li Xi, Yin Ji-Ye, Li Xiao-Lin, Zeng Hui, Chen Xiao-Ping
机构信息
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.
Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China.
出版信息
Oncotarget. 2016 Sep 13;7(37):60555-60574. doi: 10.18632/oncotarget.11143.
DNMT3A mutation is known as a recurrent event in acute myelogenous leukemia (AML) patients. However, association between DNMT3A genetic polymorphisms and AML patients' outcomes is unknown. DNMT3A 11 SNPs (rs11695471, rs2289195, rs734693, rs2276598, rs1465825, rs7590760, rs13401241, rs7581217, rs749131, rs41284843 and rs7560488) were genotyped in 344 diagnostic non-FAB-M3 AML patients from southern China. Patients underwent combined chemotherapy with cytarabine and anthracyclines. DNMT3A mRNA expression was analyzed in PBMCs from randomly selected AML patients. Multivariate analysis and combined genotype analysis showed that rs2276598 was associated with increased while rs11695471 and rs734693 were associated with decreased chemosensitivity (P<0.05), while rs11695471 (worse for OS), rs2289195 (favorable for OS and DFS) and rs2276598 (favorable for DFS) were significantly associated with disease prognosis (P<0.05). In conclusion, DNMT3A polymorphisms may be potential predictive markers for AML patients' outcomes, which might improve prognostic stratification of AML.
已知DNMT3A突变是急性髓系白血病（AML）患者中的复发性事件。然而，DNMT3A基因多态性与AML患者预后之间的关联尚不清楚。对来自中国南方的344例诊断为非FAB-M3型AML患者的DNMT3A的11个单核苷酸多态性（rs11695471、rs2289195、rs734693、rs2276598、rs1465825、rs7590760、rs13401241、rs7581217、rs749131、rs41284843和rs7560488）进行了基因分型。患者接受了阿糖胞苷和蒽环类药物的联合化疗。对随机选择的AML患者外周血单核细胞中的DNMT3A mRNA表达进行了分析。多变量分析和联合基因型分析表明，rs2276598与化疗敏感性增加相关，而rs11695471和rs734693与化疗敏感性降低相关（P<0.05），而rs11695471（总生存期较差）、rs2289195（总生存期和无病生存期良好）和rs2276598（无病生存期良好）与疾病预后显著相关（P<0.05）。总之，DNMT3A基因多态性可能是AML患者预后的潜在预测标志物，这可能改善AML的预后分层。
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