title: Frequency, onset and clinical impact of somatic DNMT3A mutations in therapy-related and secondary acute myeloid leukemia.
abstract: The recent identification of DNMT3A mutations in de novo acute myeloid leukemia prompted us to determine their frequency, patterns and clinical impact in a cohort of 98 patients with either therapy-related or secondary acute myeloid leukemia developing from an antecedent hematologic disorder. We identified 24 somatic mutations in 23 patients with a significantly higher frequency in secondary acute myeloid leukemia (35.1%) as compared to therapy-related acute myeloid leukemia (16.4%, P=0.0486). DNMT3A mutations were associated with a normal karyotype and IDH1/2 mutations, but did not affect survival. In contrast to de novo acute myeloid leukemia, most mutations did not affect arginine on position 882, but were predominantly found in the methyltransferase domain. All DNMT3A mutations identified in secondary acute myeloid leukemia were already present in the antecedent disorders indicating an early event. Reduction to homozygosity by uniparental disomy was observed in 2 patients with secondary acute myeloid leukemia during disease progression.
authors: Division of Hematology, Medical University of Graz, Austria.
authors: Isabella
authors: I
authors: Fried
authors: Claudia
authors: C
authors: Bodner
authors: Monika M
authors: MM
authors: Pichler
authors: Karin
authors: K
authors: Lind
authors: Christine
authors: C
authors: Beham-Schmid
authors: Franz
authors: F
authors: Quehenberger
authors: Wolfgang R
authors: WR
authors: Sperr
authors: Werner
authors: W
authors: Linkesch
authors: Heinz
authors: H
authors: Sill
authors: Albert
authors: A
authors: Wölfler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D014408:Biomarkers, Tumor; C000717967:DNMT3A protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A