Alterations in the genes expression profile of hematopoietic stem cell lead to pediatric B-cell acute lymphoblastic leukemia

Backgrounds: Pediatric B‑cell acute lymphoblastic lymphoma (B‑ALL) is characterized by thelymphoid progenitor cells' exponential proliferation inside the bone marrow. Numerous studiesconveyed that the tumorigenesis of B‑ALL is associated with several mutations, includingETV۶-RUNX۱, BCR‑ABL‑۱, RAS, and PI۳K, that are leading to cell cycle dysregulation. Oneof the important things to mention is that perturbation of hematopoietic stem cells (HSCs)homeostasis leads to malignancy. In this study, we analyzed online databases to find novelbiomarkers in patients with pediatric B-ALL.Materials and Methods: The GEO database was searched for pediatric B‑ALL, the expressionarray with accession number GSE۱۲۸۲۵۴ was selected. Afterward, via the GEO۲R, the data ofpatients with ALL were compared with normal controls. The genes with altered expression(|logFC| >۱) were analyzed by Cytoscape ۳.۸, and hub genes were demonstrated. Differentiallyexpressed genes (DEGs) were analyzed to reveal the genes ontology and protein-proteininteraction.Results: The KEGG pathway analyses conveyed that DEGs were strongly associated with theproteoglycans in cancer, focal adhesion, and programmed cell death. Interestingly, most of thesegenes are in the extracellular region part with protein binding function. Nine hub genes wereidentified from the PPI network in which four genes (CD۴۴, CD۳۴, TNF, and IL۱B) had apotential impact on the hematopoietic cell lineage differentiation pathway were selected.Ultimately, gene expression analyzes revealed that CD۴۴ was significantly downregulated. Onthe other hand, CD۳۴ and TNF were significantly upregulated, while the expression of IL۱B wasnot significantly altered in tumoral cells compared to normal cells.Conclusion: These results revealed that perturbations in the hematopoietic cell differentiationcould be one of the main reasons for tumorigenesis in lymphoid progenitor cells and could beserved as potential biomarkers.

Keywords:

Bioinformatics , Acute lymphoblastic lymphoma , DNA methylation