Oncotarget

Research Papers:

High expression of RUNX1 is associated with poorer outcomes in cytogenetically normal acute myeloid leukemia

Lin Fu, Huaping Fu, Lei Tian, Keman Xu, Kai Hu, Jing Wang, Jijun Wang, Hongmei Jing, Jinlong Shi and Xiaoyan Ke _

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Oncotarget. 2016; 7:15828-15839. https://doi.org/10.18632/oncotarget.7489

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Abstract

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

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     Accepted: January 24, 2016     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 (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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