학술논문
Clinical impact of DNMT3Amutations in younger adult patients with acute myeloid leukemia: results of the AML Study Group (AMLSG)
Document Type
Article
Author
Gaidzik, Verena I.; Schlenk, Richard F.; Paschka, Peter; Stölzle, Anja; Späth, Daniela; Kuendgen, Andrea; von Lilienfeld-Toal, Marie; Brugger, Wolfram; Derigs, Hans Günter; Kremers, Stephan; Greil, Richard; Raghavachar, Aruna; Ringhoffer, Mark; Salih, Helmut R.; Wattad, Mohammed; Kirchen, Heinz G.; Runde, Volker; Heil, Gerhard; Petzer, Andreas L.; Girschikofsky, Michael; Heuser, Michael; Kayser, Sabine; Goehring, Gudrun; Teleanu, Maria-Veronica; Schlegelberger, Brigitte; Ganser, Arnold; Krauter, Jürgen; Bullinger, Lars; Döhner, Hartmut; Döhner, Konstanze
Source
Blood; June 2013, Vol. 121 Issue: 23 p4769-4777, 9p
Subject
Language
ISSN
00064971; 15280020
Abstract
In this study, we evaluated the frequency and prognostic impact of DNMT3Amutations (DNMT3Amut) in 1770 younger adult patients with acute myeloid leukemia (AML) in the context of other genetic alterations and the European LeukemiaNet (ELN) classification. DNMT3Amutwere 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), NPM1mutations (P< .0001), FLT3internal tandem duplications (P< .0001), and IDH1/2mutations (P< .0001). In univariable and multivariable analyses, DNMT3Amutdid 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, DNMT3Amutrepresent 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 DNMT3Amuttype.