Identification of Genes Whose Expression Overlaps Age Boundaries and Correlates with Risk Groups in Paediatric and Adult Acute Myeloid Leukaemia

Davis, Lindsay; Mills, Ken I; Orchard, Kim H; Guinn, Barbara Ann

Abstract

Few studies have compared gene expression in paediatric and adult acute myeloid leukaemia (AML). In this study, we have analysed mRNA-sequencing data from two publicly accessible databases: (1) National Cancer Institute's Therapeutically Applicable Research to Generate Effective Treatments (NCI-TARGET), examining paediatric patients, and (2) The Cancer Genome Atlas (TCGA), examining adult patients with AML. With a particular focus on 144 known tumour antigens, we identified STEAP1, SAGE1, MORC4, SLC34A2 and CEACAM3 as significantly different in their expression between standard and low risk paediatric AML patient subgroups, as well as between poor and good, and intermediate and good risk adult AML patient subgroups. We found significant differences in event-free survival (EFS) in paediatric AML patients, when comparing standard and low risk subgroups, and quartile expression levels of BIRC5, MAGEF1, MELTF, STEAP1 and VGLL4. We found significant differences in EFS in adult AML patients when comparing intermediate and good, and poor and good risk adult AML patient subgroups and quartile expression levels of MORC4 and SAGE1, respectively. When examining Kyoto Encyclopedia of Genes and Genomes (KEGG) (2016) pathway data, we found that genes altered in AML were involved in key processes such as the evasion of apoptosis (BIRC5, WNT1) or the control of cell proliferation (SSX2IP, AML1-ETO). For the first time we have compared gene expression in paediatric AML patients with that of adult AML patients. This study provides unique insights into the differences and similarities in the gene expression that underlies AML, the genes that are significantly differently expressed between risk subgroups, and provides new insights into the molecular pathways involved in AML pathogenesis.

Citation

Davis, L., Mills, K. I., Orchard, K. H., & Guinn, B. A. (2020). Identification of Genes Whose Expression Overlaps Age Boundaries and Correlates with Risk Groups in Paediatric and Adult Acute Myeloid Leukaemia. Cancers, 12(10), 1-22. https://doi.org/10.3390/cancers12102769

• Journal Article Type: Article
• Acceptance Date: Sep 21, 2020
• Online Publication Date: Sep 27, 2020
• Publication Date: 2020-10
• Deposit Date: Sep 28, 2020
• Publicly Available Date: Sep 30, 2020
• Journal: Cancers
• Electronic ISSN: 2072-6694
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 10
• Article Number: 2769
• Pages: 1-22
• DOI: https://doi.org/10.3390/cancers12102769
• Keywords: Paediatric and adult acute myeloid leukaemia; Antigen identification; Meta-analysis; mRNA-sequencing; WNT; HOX; SOX
• Public URL: https://hull-repository.worktribe.com/output/3619428
• Publisher URL: https://www.mdpi.com/journal/cancers