Clinical Implication of DNMT3A and TET2 Genes Mutations in Cytogenetically Normal Acute Myeloid Leukemia

Document Type : Research Articles


1 Hematology Unit, Clinical Pathology Department; Mansoura University, Egypt.

2 Hematology Unit, Mansoura University, Oncology Center, Mansoura University, Egypt.


Background: Refining risk stratification of cytogenetically  normal AML (CN-AML) cases is important for decision making and tailoring of therapy. In this context genetic and epigenetic mutations was considered. Among these epigenetic regulators are DNMT3A & TET2 genes. Therefore, the aim of  this study was to determine the prevalence of DNMT3A and TET2 genes mutations and their impact on the outcome of  adult AML patients. Subjects and methods: The present study is cross sectional study which was conducted on 39 adult CN-AML patients at diagnosis. For all included patients sanger sequencing was done for DNMT3A exon 23 and TET2 exon 3 genes. Results: DNMT3A mutations were detected in 8 of 39 patients (20.5%), and in 5 of 39 patients(12.8%) in TET gene. Two CN-AML  patients had combined mutations in both genes. All of the mutations detected were missense and only one was frame shift. Mutated TET2 or DNMT3A genes were significantly associated with failure of complete remission (CR) (p <0.001), higher mortality rate, shorter OS (mean=16 versus 22.7 months) and shorter DFS (mean= 9.5 versus 21.4 months) when compared to non-mutated ones. Conclusion: Mutated TET2 and DNMT3A detection define a subgroup of CN-AML patients with poor outcome.


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