Evaluation of DNMT3A genetic polymorphisms as outcome predictors in AML patients
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Xiao-Qing Yuan1,2, Dao-Yu Zhang1,2, Han Yan1,2, Yong-Long Yang3, Ke-Wei Zhu1,2, Yan-Hong Chen1,2, Xi Li1,2, Ji-Ye Yin1,2, Xiao-Lin Li4, Hui Zeng4, Xiao-Ping Chen1,2,5
1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China
2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China
3Department of Pharmacy, Haikou People’s Hospital and Affiliated Haikou Hospital of Xiangya Medical School, Central South University, Haikou 570311, P. R. China
4Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China
5Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, P. R. China
Xiao-Ping Chen, email: email@example.com
Hui Zeng, email: firstname.lastname@example.org
Keywords: DNMT3A, polymorphism, AML, chemosensitivity, prognosis
Received: January 15, 2016 Accepted: July 26, 2016 Published: August 09, 2016
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.
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