mutation-related immune checkpoint molecule absent in melanoma 2 () contributes to immune infiltration in pediatric and adult acute myeloid leukemia: evidence from bioinformatics analysis.

BACKGROUND

The use of FMS-like tyrosine kinase 3 () as a crucial target for kinase inhibitors is well established, but its association with immune infiltration remains unclear. This study aimed to explore the relationship between mutations and immune checkpoint molecules (ICMs) in patients with acute myeloid leukemia (AML).

METHODS

The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to identify the ICMs associated with mutations. A Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) were conducted to analyze the signaling pathways related to the ICMs. The single-sample GSEA (ssGSEA), Cibersort, and estimate algorithms were used to assess immune cell infiltration in AML.

RESULTS

Absent in melanoma 2 () exhibits elevated expression levels in AML patients harboring mutation, contributing significantly to the progress of AML and establishing of an immunosuppressive microenvironment. expression significantly correlated with sensitivity of clinically relevant drugs in assays of AML. Additionally, demonstrates substantial prognostic value and holds promise as a prospective immunotherapeutic target for AML. Our findings indicate a significant correlation between and immune infiltration in AML cases, potentially affecting the presence of neutrophils, macrophages, effector memory T cells (Tem), and monocytes. Furthermore, is closely linked to various signaling pathways, such as immune cytokine release, immune antigen presentation, and inflammasome signaling, which could play a role in immune cell enrichment in AML.

CONCLUSIONS

Our study identified as an ICM linked to mutations. may be involved in the activation of suppressive immune cell populations, such as macrophages, neutrophils, and monocytes. could serve as a promising immunotherapeutic target for combination therapy with FLT3 inhibitors in AML.