Increased IL4I1 expression predicts poor survival and modulates the immune microenvironment in acute myeloid leukemia.

Jinlong Huang; Jinyuan Chen; Liangyong Yang; Zhiyong Zeng; Junfang Lin; Guilan Lai; Yanquan Liu; Xiaoqiang Zheng; Apeng Yang; Qingjiao Chen; Jinfeng Dong; Ping Chen; Junmin Chen; Liying Yu

doi:10.1186/s12967-026-07814-x

PubMed · 41680858

Increased IL4I1 expression predicts poor survival and modulates the immune microenvironment in acute myeloid leukemia.

Jinlong Huang·Jinyuan Chen·Liangyong Yang·Zhiyong Zeng·Junfang Lin·Guilan Lai·Yanquan Liu·Xiaoqiang Zheng·Apeng Yang·Qingjiao Chen·Jinfeng Dong·Ping Chen·Junmin Chen·Liying Yu

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Abstract

BACKGROUND: The immunometabolic enzyme Interleukin-4-induced-1 (IL4I1) is implicated in cancer pathogenesis, yet its specific function and clinical relevance in acute myeloid leukemia (AML) remain unclear. METHODS: Comparative analysis of IL4I1 mRNA levels between AML patients and normal controls was performed using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The Kaplan–Meier survival analysis was conducted to evaluate the prognostic value of IL4I1. Functional insights were derived from analyses of differentially expressed genes (DEGs), Gene Set Enrichment Analysis (GSEA), and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Immune infiltration was evaluated using the ssGSEA, ESTIMATE, quanTIseq and single-cell RNA sequencing (scRNA-seq) analysis. Finally, in vitro and in vivo functional experiments were perfromed to explore the impact of IL4I1 on AML progression and immunoregulation. RESULTS: IL4I1 expression was significantly elevated in AML compared to normal controls (p = 0.0004) and associated with poorer overall survival (p = 0.003). Bioinformatic analysis revealed that IL4I1 was linked to immune-related pathways—including humoral immune response, leukocyte interactions, and chemokine signaling—and to cellular amino acid metabolism. Its expression correlated with immune cell infiltration and checkpoint molecule expression. Experimentally, IL4I1 promoted leukemia cell proliferation in vitro and in vivo (p < 0.05). Furthermore, silencing IL4I1 suppressed M2 macrophage polarization and reduced secretion of inflammatory factors (p < 0.05). CONCLUSIONS: IL4I1 may serve as a potential biomarker for poor prognosis and an attractive target for immune-based therapeutic interventions in AML.

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Humans Leukemia, Myeloid, Acute Tumor Microenvironment Animals Prognosis Cell Line, Tumor Gene Expression Regulation, Leukemic Kaplan-Meier Estimate RNA, Messenger Female Cell Proliferation L-Amino Acid Oxidase Acute myeloid leukemia Biomarker IL4I1 Immune infiltration Poor prognosis Journal Article Research Support, Non-U.S. Gov't

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Jinlong Huang, Jinyuan Chen, Liangyong Yang, Zhiyong Zeng, Junfang Lin, Guilan Lai, Yanquan Liu, Xiaoqiang Zheng, Apeng Yang, Qingjiao Chen, Jinfeng Dong, Ping Chen, Junmin Chen, Liying Yu. 2026-02-12. Increased IL4I1 expression predicts poor survival and modulates the immune microenvironment in acute myeloid leukemia.. https://doi.org/10.1186/s12967-026-07814-x

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