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

作者：Fu, Lin; Shi, Jinlong; Hu, Kai; Wang, Jijun; Wang, Weidong; Ke, Xiaoyan^*

来源：Oncotarget, 2015, 6(10): 8144-8154.

DOI：10.18632/oncotarget.3519

• MAPKBP1
• prognostic biomarker
• CN-AML

Mitogen-activated protein kinase binding protein 1 (MAPKBP1) is a key transcription factor in the NF-kappa B 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 (MAPKBP1(high)) was associated with significantly shorter event-free survival (EFS; P = 0.0004) and overall survival (OS; P = 0.0006) than low MAPKBP1 expression (MAPKBP1(low)) in a cohort of 157 CN-AML patients. In multivariable analyses, MAPKBP1(high) 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 MAPKBP1(high) patients with CN-AML. MicroRNA expression profiling revealed that some oncogenic microRNAs including miR-155 and miR-126 were up-regulated, whilst anti-oncogenic microRNAs including miR-148a and miR-193a were down-regulated in MAPKBP1(high) patients with CN-AML, which may underlie the pathological processes in this malignancy. Taken together, these findings suggest MAPKBP1(high) is a novel, unfavourably prognostic biomarker for CN-AML risk-stratification.

• 出版日期2015-4-10
• 单位北京大学; 中国人民解放军总医院