title: DNMT3A R882 mutations in patients with cytogenetically normal acute myeloid leukemia and myelodysplastic syndrome.
abstract: Several molecular markers have been described that help to classify patients with acute myeloid leukemia (AML), a heterogeneous hematopoietic tissue neoplasm, into risk groups. We determined the frequency of DNMT3A mutations, their associations with clinical and molecular characteristics and outcome, in primary, cytogenetically-normal AML (CN-AML) and CN-myelodysplastic syndrome (MDS). A total of 63 CN-AML and 16 CN-MDS patients were analyzed for mutations in DNMT3A, codon R822 by direct sequencing and mutation of NPM1 and FLT3/ITD. DNMT3A mutations were found in 17/63 (27%) of CN-AML and in 1/16 (6.3%) of CN-MDS patients. Patients with DNMT3A mutations were older (p=0.047), had higher white blood cell (WBC) counts (p=0.046), more often belonged to FAB groups M4 and M5 (p=0.017), and were more associated with NPM1 mutations (p=0.017), than those with wild-type DNMT3A. DNMT3A-mutated patients had shorter overall disease survival (p<0.001) and disease-free survival (p=0.014) when the entire patient cohort was considered, which remained significant in multivariate analysis. We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in CN-AML, less frequent in CN-MDS, and that testing for R882 mutations may provide a useful tool for refining risk classification of CN-AML.
authors: Departments of Clinical Pathology, Faculty of Medicine, Mansoura University, Egypt. Electronic address: doaamahmoud1970@yahoo.com.
authors: Doaa
authors: D
authors: El Ghannam
authors: Clinical Hematology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors: Mona M
authors: MM
authors: Taalab
authors: Medical Oncology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors: Hayam F
authors: HF
authors: Ghazy
authors: Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors: Asmaa F
authors: AF
authors: Eneen
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D020732:Cytogenetic Analysis; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D000090205:DNA Methyltransferase 3A; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D000090243:Nucleophosmin; D016896:Treatment Outcome
chemical_list: C000717967:DNMT3A protein, human; C000716967:NPM1 protein, human; D000090243:Nucleophosmin; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A
keywords: Acute myeloid leukemia; DNMT3A; Leukemogenesis; Myelodysplastic syndrome; Oncogenes