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It has been recently shown that DNA methyl transferase overexpression is correlated with unfavourable prognosis in human malignancies while methylation deregulation remains a hallmark that defines acute myeloid leukemia (AML). The oncogenic transcription factor  EVI1  is involved in methylation deregulation and its overexpression plays a major role for predicting an adverse outcome. Moreover, the identification of DNMT3A mutations in AML patients has recently been described as a poor prognostic indicator. In order to clarify relationship between these key actors in methylation mechanisms and their potential impact on patient outcomes, we analysed 195  de novo  AML patients for the expression of  DNMT3A ,  3B  (and its non-catalytic variant  3B NC  ) and their correlations with the outcome and the expression of other common prognostic genetic biomarkers ( EVI1, NPM1, FLT3ITD/TKD  and  MLL ) in adult AML. The overexpression of  DNMT3B/3B NC   is (i) significantly correlated with a shorter overall survival, and (ii) inversely significantly correlated with event-free survival and  DNMT3A  expression level. Moreover, multivariate analysis showed that a high expression level of  DNMT3B/3B NC   is statistically a significant independent poor prognostic indicator. This study represents the first report showing that the overexpression of  DNMT3B/3B NC   is an independent predictor of poor survival in AML. Its quantification should be implemented to the genetic profile used to stratify patients for therapeutical strategies and should be useful to identify patients who may benefit from therapy based on demethylating agents.

High DNA Methyltransferase DNMT3B Levels: A Poor Prognostic Marker in Acute Myeloid Leukemia