<i>KRAS</i> overexpression independent of <i>RAS</i> mutations confers an adverse prognosis in cytogenetically normal acute myeloid leukemia

Abstract

The prognostic value of <i>RAS</i> mutations has been systematically investigated in acute myeloid leukemia (AML). However, clinical significance of <i>RAS</i> expressions in AML remains poorly determined. To explore the clinical significance, we analyzed <i>KRAS</i> and <i>NRAS</i> expressions in 143 <i>de novo</i> AML patients by real-time quantitative PCR. <i>KRAS</i> and <i>NRAS</i> expressions were significantly up-regulated in AML patients. <i>KRAS</i> and <i>NRAS</i> mutations were identified in 4% (6/143) and 8% (12/143) of these patients, respectively. However, no significant association was observed between <i>RAS</i> mutations and expressions. High <i>KRAS</i> expression was associated with older age, higher white blood cells, and a tendency of higher platelets, whereas high <i>NRAS</i> expression was only correlated with older age. Complete remission (CR) rate and overall survival of AML patients were adversely affected by <i>KRAS</i> overexpression, but not <i>NRAS</i> overexpression. Multivariate analysis revealed that <i>KRAS</i> acted as an independent prognostic predictor in cytogenetically normal AML (CN-AML). Moreover, the prognostic value of <i>KRAS</i> expression was validated using the published data from Gene Expression Omnibus datasets. In the follow-up patients, <i>KRAS</i> expression rather than <i>NRAS</i> expression in CR time tended to decrease compared to newly diagnosis time, and both <i>KRAS</i> and <i>NRAS</i> expressions were significantly increased when in relapse time. Our findings revealed that <i>RAS</i> overexpression and mutations were common events in AML with potential therapeutic target value. <i>KRAS</i> overexpression independent of <i>RAS</i> mutations conferred an adverse prognosis in CN-AML.