High expression of RUNX1 is associated with poorer outcomes in cytogenetically normal acute myeloid leukemia
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Lin Fu1,*, Huaping Fu3,*, Lei Tian1,*, Keman Xu4, Kai Hu1, Jing Wang1, Jijun Wang1, Hongmei Jing1, Jinlong Shi2, Xiaoyan Ke1
1Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, 100191, China
2Medical Engineering Support Center, Chinese PLA General Hospital, Beijing, 100853, China
3Department of Nuclear Medicine, Chinese PLA General Hospital, Beijing, 100853, China
4College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, 163319, China
*These authors contributed equally to this work
Jinlong Shi, e-mail: email@example.com
Xiaoyan Ke, e-mail: firstname.lastname@example.org
Keywords: RUNX1, prognostic biomarker, CN-AML
Received: October 15, 2015 Accepted: January 24, 2016 Published: February 19, 2016
Depending on its expression level, RUNX1 can act as a tumor promoter or suppressor in hematological malignancies. The clinical impact of RUNX1 expression in cytogenetically normal acute myeloid leukemia (CN-AML) remained unknown, however. We evaluated the prognostic significance of RUNX1 expression using several public microarray datasets. In the testing group (n = 157), high RUNX1 expression (RUNX1high) was associated with poorer overall survival (OS; P = 0.0025) and event-free survival (EFS; P = 0.0025) than low RUNX1 expression (RUNX1low). In addition, the prognostic significance of RUNX1 was confirmed using European Leukemia Net (ELN) genetic categories and multivariable analysis, which was further validated using a second independent CN-AML cohort (n = 162, OS; P = 0.03953). To better understand the mechanisms of RUNX1, we investigated genome-wide gene/microRNAs expression signatures and cell signaling pathways associated with RUNX1 expression status. Several known oncogenes/oncogenic microRNAs and cell signaling pathways were all up-regulated, while some anti-oncogenes and molecules of immune activation were down-regulated in RUNX1high CN-AML patients. These findings suggest RUNX1high is a prognostic biomarker of unfavorable outcome in CN-AML, which is supported by the distinctive gene/microRNA signatures and cell signaling pathways.
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