Incidence and Prognostic Influence of DNMT3A Mutations in Acute Myeloid Leukemia

• DOI: 10.1200/jco.2011.35.4894
• Publication Date: 2011-06-14T18:17:49Z
• Authors: Felicitas Thol; Frederik Damm; Andrea Lüdeking; Claudia Winschel; Katharina Wagner; Michael Morgan; Haiyang Yun; Gudrun Göhring; Brigitte Schlegel...; Dieter Hoelzer; Michael Lübbert; Lothar Kanz; Walter Fiedler; Hartmut Kirchner; Gerhard Heil; Jürgen Krauter; Arnold Ganser; Michael Heuser
• Keywords: NPM1; CEBPA

To study the incidence and prognostic impact of mutations in DNA methyltransferase 3A (DNMT3A) patients with acute myeloid leukemia.A total 489 AML were examined for DNMT3A by direct sequencing. The was evaluated context other clinical markers genetic risk factors (cytogenetic group; NPM1, FLT3, CEBPA, IDH1, IDH2, MLL1, NRAS, WT1, WT1 SNPrs16754; expression levels BAALC, ERG, EVI1, MLL5, MN1, WT1).DNMT3A found 87 (17.8%) who younger than 60 years age. Patients older, had higher WBC platelet counts, more often a normal karyotype IDH1 genes, MLL5 as compared wild-type DNMT3A. Mutations independently predicted shorter overall survival (OS; hazard ratio [HR], 1.59; 95% CI, 1.15 to 2.21; P = .005) multivariate analysis, but not associated relapse-free (RFS) or complete remission (CR) rate when entire patient cohort considered. In cytogenetically (CN) AML, 27.2% harbored that OS (HR 2.46; 1.58 3.83; < .001) lower CR (OR, 0.42; 0.21 0.84; .015), RFS (P .32). Within CN-AML, an unfavorable effect on OS, RFS, NPM1/FLT3-ITD high-risk low-risk patients.DNMT3A are frequent prognosis.