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

SIMPLE SUMMARY: To better understand whether acute myeloid leukaemia differs between children and adults, we have analysed the expression of genes in samples from both patient groups. Using previously published data, we compared gene expression between patient risk subgroups. We examined patients who had a poor chance of survival, based on clinical assessments, and those with a good chance of survival, to see whether there was any difference in the genes expressed in their leukaemic cells. Then we compared the genes on these lists between adults and children with acute myeloid leukaemia. We believe that patients with good or poor survival chances express genes that provide insights into how leukaemic cells behave. We hope that this work will provide new information about the mechanisms that underlie acute myeloid leukaemia and answer questions on the ways this form of leukaemia is similar in adults and children, which will then tell us whether the same treatments could be used for both age groups of patients. 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.