title: High expression of RUNX1 is associated with poorer outcomes in cytogenetically normal acute myeloid leukemia.
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.
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, 100191, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Nuclear Medicine, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Huaping
authors.initials: H
authors.lastname: Fu
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, 100191, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.affiliation: College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, 163319, China.
authors.forename: Keman
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, 100191, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, 100191, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, 100191, China.
authors.forename: Jijun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, 100191, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Jing
authors.affiliation: Medical Engineering Support Center, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, 100191, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human
keywords: CN-AML; RUNX1; prognostic biomarker