title: Clinical impact of DNMT3A mutations in younger adult patients with acute myeloid leukemia: results of the AML Study Group (AMLSG).
abstract: 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.
authors: Universitätsklinikum Ulm, Ulm, Germany.
authors: Verena I
authors: VI
authors: Gaidzik
authors: Richard F
authors: RF
authors: Schlenk
authors: Peter
authors: P
authors: Paschka
authors: Anja
authors: A
authors: Stölzle
authors: Daniela
authors: D
authors: Späth
authors: Andrea
authors: A
authors: Kuendgen
authors: Marie
authors: M
authors: von Lilienfeld-Toal
authors: Wolfram
authors: W
authors: Brugger
authors: Hans Günter
authors: HG
authors: Derigs
authors: Stephan
authors: S
authors: Kremers
authors: Richard
authors: R
authors: Greil
authors: Aruna
authors: A
authors: Raghavachar
authors: Mark
authors: M
authors: Ringhoffer
authors: Helmut R
authors: HR
authors: Salih
authors: Mohammed
authors: M
authors: Wattad
authors: Heinz G
authors: HG
authors: Kirchen
authors: Volker
authors: V
authors: Runde
authors: Gerhard
authors: G
authors: Heil
authors: Andreas L
authors: AL
authors: Petzer
authors: Michael
authors: M
authors: Girschikofsky
authors: Michael
authors: M
authors: Heuser
authors: Sabine
authors: S
authors: Kayser
authors: Gudrun
authors: G
authors: Goehring
authors: Maria-Veronica
authors: MV
authors: Teleanu
authors: Brigitte
authors: B
authors: Schlegelberger
authors: Arnold
authors: A
authors: Ganser
authors: Jürgen
authors: J
authors: Krauter
authors: Lars
authors: L
authors: Bullinger
authors: Hartmut
authors: H
authors: Döhner
authors: Konstanze
authors: K
authors: Döhner
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C000717967:DNMT3A protein, human; C000716967:NPM1 protein, human; D000090243:Nucleophosmin; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A