KRAS overexpression independent of RAS mutations confers an adverse prognosis in cytogenetically normal acute myeloid leukemia
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Jing-Dong Zhou1,3,*, Dong-Ming Yao2,3,*, Xi-Xi Li1,3,*, Ting-Juan Zhang1,3, Wei Zhang1,3, Ji-Chun Ma2,3, Hong Guo2,3, Zhao-Qun Deng2,3, Jiang Lin2,3 and Jun Qian1,3
1Department of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China
2Laboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China
3The Key Laboratory of Precision Diagnosis and Treatment of Zhenjiang City, Zhenjiang, Jiangsu, People’s Republic of China
*These authors have contributed equally to this work
Jun Qian, email: [email protected]
Jiang Lin, email: [email protected]
Keywords: RAS, expression, mutation, prognosis, acute myeloid leukemia
Received: April 25, 2017 Accepted: June 29, 2017 Published: August 02, 2017
The prognostic value of RAS mutations has been systematically investigated in acute myeloid leukemia (AML). However, clinical significance of RAS expressions in AML remains poorly determined. To explore the clinical significance, we analyzed KRAS and NRAS expressions in 143 de novo AML patients by real-time quantitative PCR. KRAS and NRAS expressions were significantly up-regulated in AML patients. KRAS and NRAS mutations were identified in 4% (6/143) and 8% (12/143) of these patients, respectively. However, no significant association was observed between RAS mutations and expressions. High KRAS expression was associated with older age, higher white blood cells, and a tendency of higher platelets, whereas high NRAS expression was only correlated with older age. Complete remission (CR) rate and overall survival of AML patients were adversely affected by KRAS overexpression, but not NRAS overexpression. Multivariate analysis revealed that KRAS acted as an independent prognostic predictor in cytogenetically normal AML (CN-AML). Moreover, the prognostic value of KRAS expression was validated using the published data from Gene Expression Omnibus datasets. In the follow-up patients, KRAS expression rather than NRAS expression in CR time tended to decrease compared to newly diagnosis time, and both KRAS and NRAS expressions were significantly increased when in relapse time. Our findings revealed that RAS overexpression and mutations were common events in AML with potential therapeutic target value. KRAS overexpression independent of RAS mutations conferred an adverse prognosis in CN-AML.
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