High expression of RUNX1 is associated with poorer outcomes in cytogenetically normal acute myeloid leukemia

Citations Over TimeTop 10% of 2016 papers

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.

Related Papers

• → Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling(2008)360 cited
• → Comparison of mutational profiles and clinical outcomes in patients with acute myeloid leukemia with mutated RUNX1 versus acute myeloid leukemia with myelodysplasia-related changes with mutated RUNX1(2020)11 cited
• → Evaluation of CCAAT/Enhancer Binding Protein (C/EBP) Alpha (CEBPA) and Runt‐Related Transcription Factor 1 (RUNX1) Expression in Patients with De Novo Acute Myeloid Leukemia(2017)15 cited
• → RUNX1 gene expression in Egyptian acute myeloid leukemia patients: may it have therapeutic implications?(2021)2 cited
• → Prognostic significance of CEBPA gene mutations in patients with acute myeloid leukemia(2010)