Analysis of hemolysis-associated acute myeloid leukemia genes obtained using weighted gene co-expression network analysis and a Mendelian randomization study

TL;DR

This study identifies genes linked to acute myeloid leukemia and hemolysis using bioinformatics and genetic analysis.

Contribution

The study introduces a novel integration of WGCNA and MR to explore hemolysis-related genes in AML.

Findings

Identified 190 target genes associated with AML and hemolysis through DEG, WGCNA, and GeneCards integration.

TLR4, PTPRC, FCGR3B, STAT1, and APOE were found to be closely linked to hemolysis in AML patients.

MR analysis confirmed a causal relationship between TLR4 and AML occurrence (p < 0.05).

Abstract

We used bioinformatics methods and Mendelian randomization (MR) analysis to investigate the hub genes involved in acute myeloid leukemia (AML) and their causal relationship with hemolysis, to explore a new direction for molecular biology research of AML.

We first differentially analyzed peripheral blood samples from 62 healthy volunteers and 65 patients with AML from the Gene Expression Omnibus database to obtain differentially expressed genes (DEGs), and intersected them with genes sourced from weighted gene co-expression network analysis (WGCNA) and the GeneCards database to obtain target genes. Target genes were screened using protein–protein interaction (PPI) network analysis and ROC curves to identify genes associated with AML. Finally, we analyzed the correlation between genes and immune cells and the relationship between toll-like receptor 4 (TLR4) and AML using MR.

We compared peripheral blood expression profiles using an array of 62 healthy volunteers (GSE164191) and 65 patients with AML (GSE89565) (M0:25; M1:11; M2:10; M3:1; M4:7; M4 eo t [16;16] ou inv [16]:4; M5:6; M6:1) and obtained 7,339 DEGs (3,733 upregulated and 3,606 downregulated). We intersected these DEGs with 4,724 genes from WGCNA and 1,330 genes related to hemolysis that were identified in the GeneCards database to obtain 190 target genes. After further screening these genes using the PPI network, we identified TLR4, PTPRC, FCGR3B, STAT1, and APOE, which are closely associated with hemolysis in patients with AML. Finally, we found a causal relationship between TLR4 and AML occurrence using MR analysis (p < 0.05).

We constructed a WGCNA-based co-expression network and identified hemolysis-associated AML genes.

The online version contains supplementary material available at 10.1007/s44313-025-00073-7.

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