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ORIGINAL ARTICLE
Year : 2018  |  Volume : 43  |  Issue : 4  |  Page : 193-197

Clinical relevance of DNA methyltransferase 3a (dnmt3a) mutation in patients with acute myeloid leukemia


1 Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 Medical Oncology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Correspondence Address:
Amal Zidan
Zagazig University Hospitals
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejh.ejh_3_17

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Background Acute myeloid leukemia (AML) is a complex and heterogeneous hematopoietic tissue neoplasm caused by gene mutations, chromosomal rearrangements, deregulation of gene expression, and epigenetic modifications. DNA methylation is altered in leukemia and can affect cells in three main ways: hypomethylation, hypermethylation, and loss of imprinting. Global hypomethylation has frequently been reported in the blast cells, and it is postulated that this promotes transcription of oncogenes and genes concerned with cell replication. Studies of DNA methylation in AML have revealed a series of subgroups with specific methylation signatures. Patients and methods A total of 45 patients with newly diagnosed AML were included in the study. Moreover, 45 individuals matched for age and sex were selected as controls. Immunophenotyping, conventional cytogenetic analysis, and molecular detection of DNA methyltransferase 3A (DNMT3A) exon 23 mutations were performed. Patient follow-up was performed on day 28 after receiving induction therapy to evaluate the remission status. Results DNMT3A exon 23 mutations were identified in 17.8% of patients with AML. All the mutations were missense and heterozygous. DNMT3A exon 23 mutations were significantly associated with AML with monocytic differentiation (75%) than the wild-type group (27%) (P=0.01). All DNMT3A mutations were observed in patients with intermediate-risk karyotype. There was a statistically significant decrease in the probability of achieving complete remission with shorter overall survival in the mutated group compared with the wild type, whereas no statistically significant difference between both groups in the probability of disease-free survival (P=0.14). Conclusion DNMT3A mutations are associated with poor response to therapy conferring a poor outcome, and seem to add prognostic information in patients with AML harboring it with shorter overall survival. DNMT3A mutations can represent a valuable tool for making therapeutic decisions.


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