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. 2024 Jul 1;16(1):e2024058.
doi: 10.4084/MJHID.2024.058. eCollection 2024.

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

B Altinok Gunes  1 , T Ozkan  2 , A Karadag Gurel  3 , S Dalkilic  4 , N Belder  5 , Z Ozkeserli  5 , H Ozdag  5 , M Beksac  6 , N Sayinalp  7 , A M Yagci  8 , A Sunguroglu  2
Affiliations

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

B Altinok Gunes et al. Mediterr J Hematol Infect Dis. .

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.

Keywords: AML; Beta-catenin; CD34+ cells; DEGs; Microarray.

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Conflict of interest statement

Competing interests: The authors declare no conflict of Interest.

Figures

Figure 1
Figure 1
Beta-catenin gene expression levels of AML patients.
Figure 2
Figure 2
Venn diagram analysis of DEGs. The blue circle represents the DEGs in high vs control group, the yellow circle represents the DEGs in low vs control group. The intersection of the two circles represents overlapping DEGs among the two groups. a. including up-regulated genes, b. including down-regulated genes, DEGs, differentially expressed genes.
Figure 3
Figure 3
Heat map of hierarchical cluster analysis for AML patient group with high beta-catenin levels compared to controls. Group 1 samples belong to AML patients; Group 2 samples belong to controls. Red color represents highly expressed genes; green color represents low expressed genes.
Figure 4
Figure 4
Heat map of hierarchical cluster analysis for AML patient group with low beta-catenin levels compared to controls. Group 1 samples belong to patients; Group 2 samples belong to controls. Red color represents highly expressed genes; green color represents low expressed genes.
Figure 5
Figure 5
GO enrichment analysis of up-regulated and down-regulated genes in AML patient group with high vs controls.
Figure 6
Figure 6
GO enrichment analysis of up-regulated and down-regulated genes in AML patient group with low vs controls.
Figure 7
Figure 7
KEGG pathway analysis of differentially expressed genes on cell cycle pathway in AML patient group with high beta-catenin levels vs controls. Red color represents up-regulated in AML patients.
Figure 8
Figure 8
KEGG pathway analysis of differentially expressed genes on signaling pathways regulating pluripotency of stem cells in AML patient group with low beta-catenin levels vs controls. Red color represents up-regulated in AML, green color represents down-regulated in AML patients
Figure 9
Figure 9
Venn diagram, PPI network of DEGs in High vs control a. Venn diagram of the DEGs, b. PPI network constructed with the 1194 up-regulated DEGs by the STRING, c. 1120 down-regulated DEGs were visualized by the STRING. Circles define genes, lines show protein interaction between genes. PPI, protein-protein interaction; DEGs, differentially expressed genes.
Figure 10
Figure 10
Venn diagram, PPI network of DEGs in Low vs control a. Venn diagram of the DEGs, b. PPI network constructed with the 151 up-regulated DEGs by the STRING, b. 178 down-regulated DEGs were visualized by the STRING. Circles define genes, lines show protein interaction between genes. PPI, protein-protein interaction; DEGs, differentially expressed genes.
Figure 11
Figure 11
Relationship between target gene expression and survival of patients with AML with high beta-catenin level (drawn by GEPIA).
See this image and copyright information in PMC

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