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

Oncotarget. 2015 Apr 10;6(10):8144-54. doi: 10.18632/oncotarget.3519.

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.

Keywords: CN-AML; MAPKBP1; prognostic biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics*
  • Cohort Studies
  • Cytogenetics
  • DNA Methylation
  • Female
  • Genome-Wide Association Study
  • Humans
  • Intracellular Signaling Peptides and Proteins / biosynthesis*
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Leukemia, Myeloid, Acute / enzymology*
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Middle Aged
  • Prognosis
  • Risk Factors
  • Transcriptome
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • MAPKBP1 protein, human