DNMT3A Mutations in Tunisian Patients with Acute Myeloid Leukemia

DNA Methyl Transferase 3A (DNMT3A) is one of two human de novo DNA methyltransferases essential for the regulation of gene expression. DNMT3A mutations were recently linked to hematologic malignancies prognosis. In fact, numerous mutations in this gene were reported in patients with Acute Myeloid Leukaemia (AML), pointing DNMT3A as an important oncogenic role in AML patients. In the present study, 84 patients were analyzed, at the first diagnosis for DNMT3A mutations. Exons 18, 19, 20, 21, 22 and 23 were screened by Polymerase Chain Reaction (PCR) and direct sequencing. The results demonstrated that 33.33% (28/84) de novo AML patients presented DNMT3A mutations. 9 missense mutations including 7 novel single nucleotide polymorphism resulting in amino acid substitution, one silence mutation and 1 nonsense mutation. These mutations are associated with an intermediate-risk cytogenetics (Normal Karyotype (KN-AML)), younger age, higher WBC count, bone marrow infiltration at diagnosis and lower plated count. In conclusion, we retain that the DNMT3A gene is highly mutated in the AML subgroup, its role as a prognostic factor needs to be further elucidated by correlation studies with other molecular prognosis factors and survival.