Genomic alterations, gene expression profiles, functional enrichment and prognostication of acute myeloid leukaemia-normal karyotype based on targeted next-generation sequencing

Characterising genomic variants is paramount in understanding the pathogenesis and heterogeneity of acute myeloid leukaemia- normal karyotype (AML-NK). In this study, clinically significant genomic biomarkers were ascertained using targeted DNA sequencing and RNA sequencing on eight AML-NK patients samples collected at presentation and after complete remission. In-silico and Sanger sequencing validations were performed to validate variants of interest and followed by functional and pathway enrichment analysis for overrepresentation analysis of genes with somatic variants were performed. Somatic variants involving 26 genes were identified and classified as follows: 18/42 (42.9%) as pathogenic, 4/42 (9.5%) as likely pathogenic, 4/42 (9.5%) as variants of unknown significance, 7/42(16.7%) as likely benign and 9/42(21.4%) as benign. Nine novel somatic variants were discovered, of which three were likely pathogenic, detected in the CEBPA gene with significant association with its upregulation. Transcription misregulation in cancer tops the affected pathways involving upstream genes (CEBPA and RUNX1) that were deregulated in most patients during the presentation and closely related to the most enriched molecular function gene ontology category, DNA-binding transcription activator activity RNA polymerase II-specific (GO:0001228). In summary, this study elucidated putative variants and their gene expression profiles along with functional and pathway enrichment in AML-NK patients.