Prognostic Significance of NRAS Gene Mutations in Children with Acute Myelogenous Leukemia

BACKGROUND: NRAS mutations are the most commonly detected molecular abnormalities in hematologic malignancies, especially in those of myeloid origin. OBJECTIVE: We aimed to determine the frequency of NRAS (NRAS(mutant)) mutation; and its prognostic significance in Egyptian children with acute myelogenous leukemia (AML). SUBJECT AND METHODS: Peripheral blood and bone marrow (BM) samples were taken from 39 de novo pediatric AML patients. Twenty subjects with matched age and sex were selected as a control group. Samples from patients and control were analyzed for Exons 1, 2 of NRAS gene using genomic PCR-SSCP method. RESULTS: NRAS mutations at the time of diagnosis was found in 6/39 (15.4%) AML cases. Patients with NRAS(mutant) had no significant improved clinical outcome than patients without mutation. Patients with NRAS(mutant) had similar complete remission (CR) rates compared with non-mutated patients (66.7% vs. 69.5%, P=0.43). Those in CR had a similar relapse rate regardless of the presence of NRAS(mutant) (RR 33.4% vs. 30.2%, P=0.26). However, an adverse prognosis for 3 year overall survival (OS) was associated with the presence of NRAS mutations. This adverse prognosis associated with NRAS mutations was also observed in terms of disease-free survival (DFS) (P=0.007). Univariate analysis showed that unfavorable prognostic factors for DFS were cytogenetic data (P = 0.005) and the NRAS gene mutation (P = 0.002). CONCLUSION: NRAS(mutant) did not contribute to increase the disease recurrence, however NRAS(mutant) was found to be a poor prognostic factor for children with AML. Further studies to confirm these findings are required because of the small number of patients with NRAS mutation.