DNMT3A genetic polymorphisms predict disease prognosis in R882 mutation negative AML patients

OBJECTIVE To evaluate the association between DNA(cytosine-5)-methyltransferase 3 alpha(DNMT3A)genetic polymorphisms and the disease prognosis of R882 mutation negative acute myeloid leukemia(AML)patients.METHODS DNMT3A 11 SNPs(rs11695471,rs2289195,rs734693,rs2276598,rs1465825,rs7590760,rs13401241,rs7581217,rs749131,rs41284843 and rs7560488)were genotyped using a MassA RRAY platform or Sanger sequencing method in 317 diagnostic non-FABM3 AML patients without R882 mutation from southern China.AML patients underwent combined chemotherapy with cytarabine and anthracyclines.Overall survival(OS)and Disease-free survival(DFS)as major end points were defined.The prognostic(median OS and DFS)evaluations were performed by Kaplan-Meier curve and Cox′s proportional hazard model.RESULTS We found that the rs2289195 G>A SNP could act as a poor prognostic predictor independently(HR=0.442,P=0.035 for OS;HR=0.431,P=0.031 for DFS),while the rs1465825 T>C SNP and rs7590760 G>C SNP appeared to predict independently poor prognosis for both OS(HR=1.453,P=0.037 for rs1465825;HR=1.584,P=0.063 for rs7590760)and DFS(HR=1.459,P=0.057 for rs1465825;HR=1.965,P=0.017for rs7590760).However,no significant associations between other DNMT3A polymorphisms and prognosis(OS in conjunction with DFS)were observed.CONCLUSION DNMT3A polymorphisms may be potential predictive markers for AML prognosis in R882 mutation negative patients,which might improve prognostic stratification of AML.