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OBJECTIVE To evaluate the association between DNMT3A,DNMT3B and SETD2 genetic variations and the chemosensitivity and disease prognosis of acute myeloid leukemia (AML) patients.METHODS DNMT3A R882 mutations,DNMT3B five SNPs and SETD2 six SNPs were genotyped using a MassARRAY platform or sequencing in 344 diagnostic non-M3 AML patients from southern China.The expression of DNMT3B mRNA and miR-30s was analyzed in PBMCs from randomly selected AML patients and healthy subjects.AML patients underwent combined chemotherapy with cytarabine and anthraeyelines.Complete remission (CR),Overall survival (OS) and Disease-free survival (DFS) as major end points were defined.The chemosensitivity (CR rate) was assessed by x2 test and logistic regression model,while the prognosis (median OS and DFS) was evaluated by Kaplan-Meier curve and Coxs proportional hazard model.RESULTS Multivariate logistic regression analysis showed that both DNMT3B rs6058896 C>T and SETD2 rs4082155 A>G presented a favorable chemotherapy response independently (P<0.05).Survival analysis verified that the DNMT3A R882 mutation AML patients showed markedly poorer prognosis compared with R882 wildtype patients (P<0.0001 for O S;P<0.01 for DFS),and we firstly found that the AML patients with higher R882 mutation percentage showed significantly shorter median OS (P<0.05).Multivariate cox regression analysis indicated that DNMT3B rs742630 G>C and SETD2 rs4082155 A>G could act as a favorable and prognostic predictor independently (P<0.05),while DNMT3B rs6058896 C>T appeared to predict independently poor prognosis (P<0.05).In addition,DNMT3B mRNA levels were markedly higher in AML patients than those in healthy volunteers (P<0.01),but miR-30s expression was greatly lower in AML patients (P<0.001).CONCLUSION DNMT-3A/-3B and SETD2 genetic variations could be potential predictive markers for AML outcomes in south Chinese population.Abnormal expression of DNMT3B and miR-30s may involve in the pathogenesis of AML,which remains to be further validation.