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 ) 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   had no significant  improved clinical  outcome than patients without mutation. Patients with NRAS  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 ofNRAS  (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  did not contribute to increase the disease recurrence, however NRAS  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.