Evaluation of DNMT3A genetic polymorphisms as outcome predictors in AML patients

// Xiao-Qing Yuan 1, 2 , Dao-Yu Zhang 1, 2 , Han Yan 1, 2 , Yong-Long Yang 3 , Ke-Wei Zhu 1, 2 , Yan-Hong Chen 1, 2 , Xi Li 1, 2 , Ji-Ye Yin 1, 2 , Xiao-Lin Li 4 , Hui Zeng 4 , Xiao-Ping Chen 1, 2, 5 1 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China 2 Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China 3 Department of Pharmacy, Haikou People’s Hospital and Affiliated Haikou Hospital of Xiangya Medical School, Central South University, Haikou 570311, P. R. China 4 Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China 5 Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, P. R. China Correspondence to: Xiao-Ping Chen, email: chenxp74@hotmail.com Hui Zeng, email: androps2011@hotmail.com Keywords: DNMT3A, polymorphism, AML, chemosensitivity, prognosis Received: January 15, 2016     Accepted: July 26, 2016     Published: August 09, 2016 ABSTRACT 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.