Distinct association of RUNX family expression with genetic alterations and clinical outcome in acute myeloid leukemia
Article type: Research Article
Authors: Zhao, Yanglia; b; c; 1 | Zhang, Tingjuana; c; d; e; 1 | Zhao, Yangjingf; * | Zhou, Jingdonga; c; d; e; *
Affiliations: [a] Department of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China | [b] Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, Jiangsu, China | [c] Zhenjiang Medical School, Nanjing Medical University, Zhenjiang, Jiangsu, China | [d] Zhenjiang Clinical Research Center of Hematology, Zhenjiang, Jiangsu, China | [e] The Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang City, Zhenjiang, Jiangsu, China | [f] Department of Immunology, Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, China
Correspondence: [*] Corresponding authors: Yangjing Zhao, Department of Immunology, Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China. E-mail: zyjjsls2008@163.com. Jingdong Zhou, Department of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang Medical School, Nanjing Medical University, 8 Dianli Rd., Zhenjiang, Jiangsu, China. E-mail: zhoujingdong1989@qq.com.
Note: [1] These authors contributed equally to this work.
Abstract: BACKGROUND: The runt-related transcription factor family (RUNXs) including RUNX1, RUNX2, and RUNX3 are key transcriptional regulators in normal hematopoiesis. RUNXs dysregulations caused by aberrant expression or mutation are frequently seen in various human cancers especially in acute myeloid leukemia (AML). OBJECTIVE: We systemically analyzed the expression of RUNXs and their relationship with clinic-pathological features and prognosis in AML patients. METHODS: Expression of RUNXs was analyzed between AML patients and normal controls from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects. Correlations between RUNXs expression and clinical features together with survival were further analyzed. RESULTS: All RUNXs expression in AML patients was significantly increased as compared with controls. RUNXs expression was found to be significantly associated with genetic abnormalities such as RUNX1 mutation, t(8;21) and inv(16)/t(16;16). By Kaplan-Meier analysis, only RUNX3 overexpression was associated with shorter overall survival (OS) and disease-free survival (DFS) among non-M3 AML patients. Notably, in high RUNX3 expression groups, patients received hematopoietic stem cell transplantation (HSCT) had markedly better OS and DFS than patients without HSCT among both all AML and non-M3 AML. In low RUNX3 expression groups, there were no significant differences in OS and DFS between HSCT and non-HSCT groups among both all AML and non-M3 AML. In addition, a total of 835 differentially expressed genes and 69 differentially expressed microRNAs were identified to be correlated with RUNX3 expression in AML. CONCLUSION:RUNXs overexpression was a frequent event in AML, and was closely associated with diverse genetic alterations. Moreover, RUNX3 expression may be associated with clinical outcome, and helpful for guiding treatment choice between HSCT and chemotherapy in AML.
Keywords: RUNX, expression, prognosis, biomarker, acute myeloid leukemia
DOI: 10.3233/CBM-200016
Journal: Cancer Biomarkers, vol. 29, no. 3, pp. 387-397, 2020
