Prognostic features of NRAS missense mutations in adult acute myeloid leukemia patients

Abstract

The aim of the study was to assess the prognostic significance of missense mutations in the NRAS gene in adult patients with acute myeloid leukemia (AML). Clinical observation was performed on 70 patients with AML. The average age of the examined was 52.0 ± 3.4 years. NRAS gene point mutations were detected using direct sequencing technique. According to the results of cytogenetic, immunohistochemical and PCR studies, a favorable prognosis was determined in 18 cases (25.7%), an intermediate in 15 (21.4%), and an unfavorable one in 18 cases (25.7%). In 19 samples (27.1%) genetic anomalies could not be detected; accordingly, the prognosis option for such patients was not specified. NRAS missense mutations were represented by T17A, C181A, A182C transversions (5 cases) and G35A, G38A transitions (3 cases), and a synonymous (silent) G360A substitution (1 case). Average frequency of prognostically significant NRAS mutations was 11.4%. All the above non-synonymous mutations were localized in exons 1-3, which caused the blocking of the internal GTPase activity of the N-ras protein and its stabilization in the active state. Clinically, all NRAS-positive AMLs were characterized by an unfavorable prognosis and primary tumor resistance to chemotherapy. The average follow-up of patients was 8.4 ± 8.2 months.