Convergent Multistage Evidence Implicates the CCR2–Artemin Immune–Inflammation Axis in Acute Myeloid Leukemia
Yi Jin, Hui-Min Lu, Xing-Hao Yu, Ming-Zhu Su, Jun Li, Xiao-Min Li, Jian-Hua Jin, Li-Ting Zhang, Yue Wang
TL;DR
This study identifies a new immune-inflammation pathway involving CCR2 and artemin that may influence the risk of acute myeloid leukemia.
Contribution
The study provides novel mechanistic evidence linking the CCR2–Artemin axis to AML risk through integrative genetic and experimental approaches.
Findings
CCR2 on CD62L+ myeloid dendritic cells is associated with lower AML risk.
Artemin mediates the CCR2–AML association, supported by CCR2 inhibition increasing ARTN mRNA.
Proteomic correlations link ARTN to immune-metabolic proteins like CLEC6A and SIGLEC6.
Abstract
The immune system and inflammatory proteins influence hematologic malignancies, but causal links with immune cell phenotypes are unclear. We applied a prespecified, multistage workflow: two‐sample and multivariable Mendelian randomization (MVMR; 731 immune traits across 12 hematologic cancers), two‐step mediation Mendelian randomization (MR) of 91 circulating inflammatory proteins, MAGMA/FUMA gene and pathway enrichment, and external validation with trait‐specific genetic risk scores (GRSs) in UK Biobank (UKB). We then performed CCR2 perturbation assays in human monocytic leukemia cell line (THP‐1) and immortalized bone marrow‐derived macrophage (IBMDM) cells with artemin (ARTN) mRNA readouts and examined proteomic correlations for ARTN using the Olink inflammatory panel. Eight immune phenotypes showed FDR–significant causal associations with malignancy, seven of which remained…
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Taxonomy
TopicsAcute Myeloid Leukemia Research · Immune cells in cancer · Ferroptosis and cancer prognosis