TitleMutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia.
Publication TypeJournal Article
Year of Publication2012
AuthorsRibeiro, Ana Flávia Ti, Pratcorona Marta, Erpelinck-Verschueren Claudia, Rockova Veronika, Sanders Mathijs, Abbas Saman, Figueroa Maria E., Zeilemaker Annelieke, Melnick Ari, Löwenberg Bob, Valk Peter J. M., and Delwel Ruud
Date Published2012 Jun 14
KeywordsAdolescent, Adult, Biomarkers, Tumor, Cluster Analysis, DNA (Cytosine-5-)-Methyltransferases, DNA Methylation, DNA Methyltransferase 3A, Female, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Humans, Leukemia, Myeloid, Acute, Male, Middle Aged, Multivariate Analysis, Mutant Proteins, Mutation, Neoplasm Proteins, Nucleophosmin, Prognosis, Recurrence, Survival Analysis, Treatment Outcome, Young Adult

<p>The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. We show mutations in DNMT3A in 96 of 415 patients with newly diagnosed AML (23.1%). Univariate Cox regression analysis showed that patients with DNMT3A(mutant) AML show significantly worse overall survival (OS; P = .022; hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.04-1.81), and relapse-free survival (RFS; P = .005; HR, 1.52; 95% CI, 1.13-2.05) than DNMT3A(wild-type) AMLs. In a multivariable analysis, DNMT3A mutations express independent unfavorable prognostic value for OS (P = .003; HR, 1.82; 95% CI, 1.2-2.7) and RFS (P < .001; HR, 2.2; 95% CI, 1.4-3.3). In a composite genotypic subset of cytogenetic intermediate-risk AML without FLT3-ITD and NPM1 mutations, this association is particularly evident (OS: P = .013; HR, 2.09; 95% CI, 1.16-3.77; RFS: P = .001; HR, 2.65; 95% CI, 1.48-4.89). The effect of DNMT3A mutations in human AML remains elusive, because DNMT3A(mutant) AMLs did not express a methylation or gene expression signature that discriminates them from patients with DNMT3A(wild-type) AML. We conclude that DNMT3A mutation status is an important factor to consider for risk stratification of patients with AML.</p>

Alternate JournalBlood
PubMed ID22490330