Mitogen-activated protein kinase binding protein 1 (MAPKBP1) is an unfavorable prognostic biomarker in cytogenetically normal acute myeloid leukemia.
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.
Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, China.
Lin
L
Fu
Medical Engineering Support Center, Chinese PLA General Hospital, Beijing, China.
Jinlong
J
Shi
Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, China.
Kai
K
Hu
Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, China.
Jijun
J
Wang
Medical Engineering Support Center, Chinese PLA General Hospital, Beijing, China.
Weidong
W
Wang
Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, China.
Xiaoyan
X
Ke
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics*; D015331:Cohort Studies; D003582:Cytogenetics; D019175:DNA Methylation; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D059467:Transcriptome; D055815:Young Adult
D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C580778:MAPKBP1 protein, human
CN-AML; MAPKBP1; prognostic biomarker