Oncotarget

Research Papers:

Mitogen-activated protein kinase binding protein 1 (MAPKBP1) is an unfavorable prognostic biomarker in cytogenetically normal acute myeloid leukemia

Lin Fu, Jinlong Shi, Kai Hu, Jijun Wang, Weidong Wang and Xiaoyan Ke _

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Oncotarget. 2015; 6:8144-8154. https://doi.org/10.18632/oncotarget.3519

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Abstract

Lin Fu1,*, Jinlong Shi2,*, Kai Hu1, Jijun Wang1, Weidong Wang2 and Xiaoyan Ke1

1 Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, China

2 Medical Engineering Support Center, Chinese PLA General Hospital, Beijing, China

* These authors contributed equally to this work

Correspondence to:

Xiaoyan Ke, email:

Weidong Wang, email:

Keywords: MAPKBP1, prognostic biomarker, CN-AML

Received: January 08, 2015 Accepted: February 03, 2015 Published: March 10, 2015

Abstract

Mitogen-activated protein kinase binding protein 1 (MAPKBP1) is a key transcription factor in the NF-κB signalling pathway. In this study, associations between MAPKBP1 expression and molecular and clinical characteristics were evaluated by several microarray datasets. We found that MAPKBP1 was over-expressed in cytogenetically normal AML (CN-AML) patients compared to normal bone marrow. High MAPKBP1 expression (MAPKBP1high) was associated with significantly shorter event-free survival (EFS; P = 0.0004) and overall survival (OS; P = 0.0006) than low MAPKBP1 expression (MAPKBP1low) in a cohort of 157 CN-AML patients. In multivariable analyses, MAPKBP1high remained associated with shorter EFS (P = 0.003) and OS (P = 0.01). Validation in an independent cohort of 162 CN-AML patients further confirmed the prognostic value of MAPKBP1 (OS, P = 0.00172). Gene-expression profiling revealed that some important oncogenes, including MYCN, MYB, CDK6 and CCND2, etc, were up-regulated, while cell signalling pathways leading to apoptosis, antigen processing, and natural killer cell-mediated cytotoxicity were down-regulated in MAPKBP1high patients with CN-AML. MicroRNA expression profiling revealed thatsome oncogenic microRNAsincluding miR-155 and miR-126 were up-regulated, whilst anti-oncogenic microRNAsincluding miR-148a and miR-193a were down-regulated in MAPKBP1high patients with CN-AML, which may underlie the pathological processes in this malignancy. Taken together, these findings suggest MAPKBP1highis a novel, unfavourably prognostic biomarker for CN-AML risk-stratification.


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