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Clinical impact of DNMT3A mutations in younger adult patients with acute myeloid leukemia: results of the AML Study Group (AMLSG)

2013; Elsevier BV; Volume: 121; Issue: 23 Linguagem: Inglês

10.1182/blood-2012-10-461624

1528-0020

Verena I. Gaidzik, Richard F. Schlenk, Peter Paschka, Anja Stölzle, Daniela Späth, Andrea Kuendgen, Marie von Lilienfeld‐Toal, Wolfram Brugger, Hans Günter Derigs, Stephan Kremers, Richard Greil, Aruna Raghavachar, Mark Ringhoffer, Helmut R. Salih, Mohammed Wattad, Heinz Kirchen, Volker Runde, Gerhard Heil, Andreas Petzer, Michael Girschikofsky, Michael Heuser, Sabine Käyser, Gudrun Goehring, Maria‐Veronica Teleanu, Brigitte Schlegelberger, Arnold Ganser, Jürgen Krauter, Lars Bullinger, Hartmut Döhner, Konstanze Döhner,

Acute Lymphoblastic Leukemia research

In this study, we evaluated the frequency and prognostic impact of DNMT3A mutations (DNMT3A(mut)) in 1770 younger adult patients with acute myeloid leukemia (AML) in the context of other genetic alterations and the European LeukemiaNet (ELN) classification. DNMT3A(mut) were found in 20.9% of AMLs and were associated with older age (P < .0001), higher white blood cell counts (P < .0001), cytogenetically normal AML (CN-AML; P < .0001), NPM1 mutations (P < .0001), FLT3 internal tandem duplications (P < .0001), and IDH1/2 mutations (P < .0001). In univariable and multivariable analyses, DNMT3A(mut) did not impact event-free, relapse-free (RFS), or overall survival (OS) in either the entire cohort or in CN-AML; a negative prognostic effect was found only in the ELN unfavorable CN-AML subset (OS, P = .011). In addition, R882 mutations vs non-R882 mutations showed opposite clinical effects-unfavorable for R882 on RFS (all: hazard ratio [HR], 1.29 [P = .026]; CN-AML: HR, 1.38 [P = .018]) and favorable for non-R882 on OS (all: HR, 0.77 [P = .057]; CN-AML: HR, 0.73 [P = .083]). In our statistically high-powered study with minimized selection bias, DNMT3A(mut) represent a frequent genetic lesion in younger adults with AML but have no significant impact on survival end points; only moderate effects on outcome were found, depending on molecular subgroup and DNMT3A(mut) type.