Bioinformatics Analysis of Differentially Expressed Genes and Their Functional Enrichment in Acute Myeloid Leukemia Bearing MLL Translocation

Yongjin Tang,Jinyuan Zheng,Yang Chen,Donghong Lin,Xiaomeng Fu

doi:10.36648/2472-1646.5.2.60

Abstract

Background: Chromosomal translocations of the mixed-lineage leukemia gene (MLL; tMLL) correlate with resistance to therapy and an extremely poor prognosis for individuals with Acute Myeloid Leukemia (AML). The underlying mechanisms are still unknown. This study aims to identify the key genes and the potential molecular mechanisms involved in MLL rearrangement in AML using a bioinformatics approach. Methods: The gene expression profiles from 15 individuals with partial tandem duplication of the MLL gene (MLL-PTD)-AML and 10 tMLL-AML samples were downloaded from the Gene Expression Omnibus (GEO) database. The Differentially Expressed Genes (DEGs) were selected and functional enrichment analyses were performed. The Protein-Protein Interaction (PPI) network was established and visualized in Cytoscape. The hub genes were identified by CytoHubba and significant modules were screened out by Molecular Complex Detection (MCODE). Results: We categorized a total of 885 DEGs comprising 330 upregulated and 555 downregulated genes. The majority of DEGs were significantly enriched for calcium ion transmembrane transport, embryonic skeletal system morphogenesis and cell proliferation processes. Several pathways were enriched, including those associated with PI3K-Akt signaling and insulin resistance. We identified 32 hub genes and screened out 2 modules. Conclusion: The genes we have identified in this study may represent potential biomarkers for MLL-rearranged AML and contribute to the development of novel therapeutic strategies.

Highlights

We aimed to identify Differentially Expressed Genes (DEGs) by comparing mixed-lineage leukemia gene (MLL)-Partial Tandem Duplication (PTD) and the mixed-lineage leukemia (tMLL) data from the Gene Expression Omnibus (GEO) database
The Gene Ontology (GO) Biological Process (BP) function of the Database for Annotation (DAVID) tool revealed that the upregulated DEGs were significantly enriched in calcium ion transmembrane transport, cilium assembly and osteoblast differentiation processes
Our study showcases preliminary research into the mechanisms involved in Acute Myeloid Leukemia (AML) bearing MLL translocations

Summary

Introduction

The majority of AML patients bear abnormal chromosomal karyotypes. Cytogenetic abnormalities such as chromosomal translocations involving the mixed-lineage leukemia gene (MLL) are associated with a poor prognosis for AML patients [1]. A small subset of AML patients develops treatment-induced secondary leukemias, in which the MLL gene may be rearranged to generate Partial Tandem Duplication (PTD), amplification, or fused to a partner gene through a chromosomal translocation (tMLL) [2]. Chromosomal translocations of the mixed-lineage leukemia gene (MLL; tMLL) correlate with resistance to therapy and an extremely poor prognosis for individuals with Acute Myeloid Leukemia (AML). This study aims to identify the key genes and the potential molecular mechanisms involved in MLL rearrangement in AML using a bioinformatics approach

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