Transcriptome Analysis of Beta-Catenin-Related Genes in CD34+ Haematopoietic Stem and Progenitor Cells from Patients with AML.

ABSTRACT

Background: Acute myeloid leukaemia (AML) is a disease of the haematopoietic stem cells(HSCs) that is characterised by the uncontrolled proliferation and impaired differentiation of normal haematopoietic stem/progenitor cells. Several pathways that control the proliferation and differentiation of HSCs are impaired in AML. Activation of the Wnt/beta-catenin signalling pathway has been shown in AML and beta-catenin, which is thought to be the key element of this pathway, has been frequently highlighted. The present study was designed to determine beta-catenin expression levels and beta-catenin-related genes in AML. Methods: In this study, beta-catenin gene expression levels were determined in 19 AML patients and 3 controls by qRT-PCR. Transcriptome analysis was performed on AML grouped according to beta-catenin expression levels. Differentially expressed genes(DEGs) were investigated in detail using the Database for Annotation Visualisation and Integrated Discovery(DAVID), Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG), STRING online tools. Results: The transcriptome profiles of our AML samples showed different molecular signature profiles according to their beta-catenin levels(high-low). A total of 20 genes have been identified as hub genes. Among these, TTK, HJURP, KIF14, BTF3, RPL17 and RSL1D1 were found to be associated with beta-catenin and poor survival in AML. Furthermore, for the first time in our study, the ELOV6 gene, which is the most highly up-regulated gene in human AML samples, was correlated with a poor prognosis via high beta-catenin levels. Conclusion: It is suggested that the identification of beta-catenin-related gene profiles in AML may help to select new therapeutic targets for the treatment of AML.