High expression of <i>RUNX1</i> is associated with poorer outcomes in cytogenetically normal acute myeloid leukemia

Abstract

// Lin Fu 1, * , Huaping Fu 3, * , Lei Tian 1, * , Keman Xu 4 , Kai Hu 1 , Jing Wang 1 , Jijun Wang 1 , Hongmei Jing 1 , Jinlong Shi 2 , Xiaoyan Ke 1 1 Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, 100191, China 2 Medical Engineering Support Center, Chinese PLA General Hospital, Beijing, 100853, China 3 Department of Nuclear Medicine, Chinese PLA General Hospital, Beijing, 100853, China 4 College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, 163319, China * These authors contributed equally to this work Correspondence to: Jinlong Shi, e-mail: jinlong_301@163.com Xiaoyan Ke, e-mail: xiaoyank@yahoo.com Keywords: RUNX1, prognostic biomarker, CN-AML Received: October 15, 2015&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: January 24, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: February 19, 2016 ABSTRACT 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 ( RUNX1 high ) was associated with poorer overall survival (OS; P = 0.0025) and event-free survival (EFS; P = 0.0025) than low RUNX1 expression ( RUNX1 low ). 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 RUNX1 high CN-AML patients. These findings suggest RUNX1 high is a prognostic biomarker of unfavorable outcome in CN-AML, which is supported by the distinctive gene/microRNA signatures and cell signaling pathways.