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Frequency, onset and clinical impact of somatic DNMT3A mutations in therapy-related and secondary acute myeloid leukemia.
- Source :
-
Haematologica [Haematologica] 2012 Feb; Vol. 97 (2), pp. 246-50. Date of Electronic Publication: 2011 Oct 11. - Publication Year :
- 2012
-
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.
- Subjects :
- Aged
Aged, 80 and over
Cohort Studies
DNA Methyltransferase 3A
Female
Humans
Leukemia, Myeloid, Acute epidemiology
Male
Middle Aged
Neoplasms, Second Primary epidemiology
Biomarkers, Tumor genetics
DNA (Cytosine-5-)-Methyltransferases genetics
Leukemia, Myeloid, Acute genetics
Mutation genetics
Neoplasms, Second Primary genetics
Polymorphism, Single Nucleotide
Subjects
Details
- Language :
- English
- ISSN :
- 1592-8721
- Volume :
- 97
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- 21993668
- Full Text :
- https://doi.org/10.3324/haematol.2011.051581