Evaluation of Expression Profile of Patients with Acute Myeloid Leukemia in Response to Azacitidine with Biological System Approach.

Abstract

Acute myeloid leukemia (AML) is a prevalent type of leukemia that is associated with high rates of chemoresistance, including resistance to Azacitidine (AZA). Understanding the molecular mechanisms of chemoresistance can lead to the development of novel therapeutic approaches. In this study, we aimed to identify dysregulated miRNAs and their target genes involved in chemoresistance to AZA in AML patients. We analyzed expression profiles from two GEO datasets (GSE16625 and GSE77750) using the "Limma" package in R. We identified 29 differentially expressed miRNAs between AML patients treated with AZA and healthy individuals. MultiMiR package of R was used to predict target genes of identified miRNAs, and functional enrichment analysis was performed using FunRich software. Protein-protein interaction networks were constructed using STRING and visualized using Cytoscape. MiR-582 and miR- 597 were the most up- and down-regulated miRNAs, respectively. Functional enrichment analysis revealed that metal ion binding, regulation of translation, and proteoglycan syndecan-mediated signaling events were the most enriched pathways. The tumor necrosis factor (TNF) gene was identified as a hub gene in the protein-protein interaction network. Our study identified dysregulated miRNAs and their target genes in response to AZA treatment in AML patients. These findings provide insights into the molecular mechanisms of chemoresistance and suggest potential therapeutic targets for the treatment of AML. Further experimental validation of the identified miRNAs and their targets is warranted.