Mutant DNMT3A: A marker of poor prognosis in acute myeloid leukemia

Ana Flávia Tibúrcio Ribeiro, Marta Pratcorona, Claudia Erpelinck-Verschueren, Veronika Rockova, Mathijs Sanders, Saman Abbas, Maria E. Figueroa, Annelieke Zeilemaker, Ari Melnick, Bob Löwenberg, Peter J.M. Valk, Ruud Delwel

Research output: Contribution to journalArticlepeer-review

177 Scopus citations

Abstract

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 DNMT3Amutant 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 DNMT3Awild-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 DNMT3Amutant AMLs did not express a methylation or gene expression signature that discriminates them from patients with DNMT3Awild-type AML. We conclude that DNMT3A mutation status is an important factor to consider for risk stratification of patients with AML.

Original languageEnglish (US)
Pages (from-to)5824-5831
Number of pages8
JournalBlood
Volume119
Issue number24
DOIs
StatePublished - Jun 14 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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