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High expression of RUNX1 is associated with poorer outcomes in cytogenetically normal acute myeloid leukemia
- Source :
- Oncotarget
- Publication Year :
- 2016
- Publisher :
- Impact Journals, LLC, 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.
- Subjects :
- Adult
Male
0301 basic medicine
RUNX1
Adolescent
Microarray
Kaplan-Meier Estimate
CN-AML
Bioinformatics
Disease-Free Survival
law.invention
Young Adult
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Text mining
law
hemic and lymphatic diseases
microRNA
Biomarkers, Tumor
medicine
Humans
prognostic biomarker
Gene
Aged
business.industry
Middle Aged
Prognosis
medicine.disease
Leukemia, Myeloid, Acute
Leukemia
030104 developmental biology
Oncology
chemistry
030220 oncology & carcinogenesis
Core Binding Factor Alpha 2 Subunit
embryonic structures
Cohort
Cancer research
Suppressor
Female
business
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....334cda2363308bfc4100c947408c7b2b