Identification of intrinsically disordered regions in hub genes of acute myeloid leukemia: A bioinformatics approach

Abstract

Acute myeloid leukemia (AML) is the most common acute leukemia in adults.Over the past decades, there has been a great challenge in the treatment of AML. A combination of gene expression profiling with computational approaches can lead to the identification of hub genes in AML. However, it is important to study the structure of these hub genes considering their importance in the proteinprotein interaction (PPI) network of specific cancer. In this study, we designed an integrated method to analyze the presence of intrinsically disordered regions (IDRs) in selected hub genes of AML. A gene expression profile of AML was obtained from Gene Expression Omnibus (GEO) database. Further analysis identified differentially expressed genes (DEGs) in AML. Additionally, the top 15 hub genes following construction and analysis of the PPI network of DEGs were selected. Validation of hub genes revealed that there is a reverse relationship between overexpression of FLT3, PPBP, and PF4 genes and the survival of AML patients. Based on IDRs investigation, FLT3 and PF4 are partially disordered, while PPBP is mostly disordered. Through clustering the network into structural modules, we identified two important modules in the PPI network of DEGs that showed the important position of PPBP in module 1. Based on further analysis of protein flexibility and its important role in biological processes, we suggest that PPBP can be considered as a potential drug target in AML. K E Y W O R D Sacute myeloid leukemia (AML), hub genes, intrinsically disordered regions (IDRs), PPI network Abbreviations: AML, Acute myeloid leukemia; PPI, protein-protein interaction; IDRs, intrinsically disordered regions; GEO, gene expression omnibus; DEGs, differentially expressed genes; BM, bone marrow; PB, peripheral blood; allo-HSCT, allogeneic hematopoietic stem cell transplantation; KEGG, kyoto encyclopedia of genes and genomes; GEPIA, gene expression profiling interactive analysis.

Transcriptome Analysis in Mexican Adults with Acute Lymphoblastic Leukemia

“…PPBP has been involved in various cellular processes and malignancies [48][49][50][51]; in fact, it has been found to be down-regulated in the plasma of patients with gastric cancer (GC), and has been suggested to be a diagnostic biomarker of that disease [49,52]. Our combination of gene expression profiling with a computational approach using STRING showed PPBP to be a hub gene in ALL, as has been observed in AML, and based on its important role in biological processes, PPBP could be considered a potential drug target in acute leukemias [53,54].…”

Advancements in Myeloid Leukemia Treatment: A Comprehensive Update

“…Alterations in DNA methylation and histone modifications have been implicated in the dysregulation of gene expression in AML. The identification of intrinsically disordered regions in hub genes of AML has provided insights into the protein-protein interaction networks and gene expression profiles associated with the disease [84] [85].…”