ArticleBlood2023
TREM2 acts as a receptor for IL-34 to suppress acute myeloid leukemia in mice.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- FGF18 mediates fibroblast-leukemia cross talk to promote acute myeloid leukemia progression.Blood · 2026Article
- Cytokine multimerization: when more is more and sometimes less.Nature reviews. Immunology · 2026Review
- Crosstalk between bone and vasculature within bone.Fundamental research · 2026Review
- TREM2 inhibits cholangiocarcinoma progression by regulating the TGF-β/Smad2/3 signaling pathway.American journal of cancer research · 2026Article
- IL-34 in neurological homeostasis and its multifaceted roles in central nervous system diseases.Frontiers in immunology · 2026Review
- Roles of IL-34 in neurological diseases: neuroprotection, inflammatory regulation, and myeloid plasticity.Frontiers in immunology · 2026Review
- Macrophage Trem2 deficiency aggravates aging-induced vascular remodeling by acting as a non-classical receptor of interleukin-13.Molecular biomedicine · 2025Article
- Role of TREM2 in neuroinflammation regulation: mechanisms, disease associations, and therapeutic translation advances.Journal of translational medicine · 2025Review
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
- Macrophage/microglia-dependent mechanisms drive retinal pigment epithelium regeneration in zebrafish.Cell reports · 2025Article
- MAP4K signaling pathways in cancer: roles, mechanisms and therapeutic opportunities.Experimental & molecular medicine · 2025Review
- Mutation in the rat interleukin 34 gene impacts macrophage development, homeostasis, and inflammation.Life science alliance · 2025Article
- The role and mechanism of TSC in kidney diseases: a literature review.BMC nephrology · 2025Review
- Targeting the IL34-CSF1R axis improves metastatic renal cell carcinoma therapy outcome via immune-vascular crosstalk regulation.iScience · 2025Article
- TREML2 enhances sensitivity of acute myeloid leukemia cells to chemotherapy by inhibiting the NF-κB/CXCL10 pathway.Blood science (Baltimore, Md.) · 2025Article
- From Chemotherapy to Targeted Therapy: Unraveling Resistance in Acute Myeloid Leukemia Through Genetic and Non-Genetic Insights.International journal of molecular sciences · 2025Review
- Interleukin-34 and debris clearance by mononuclear phagocytes drive retinal pigment epithelium regeneration in zebrafish.bioRxiv : the preprint server for biology · 2025Article
- Biophysical mapping of TREM2-ligand interactions reveals shared surfaces for engagement of multiple Alzheimer's disease ligands.Molecular neurodegeneration · 2025Article
- Interleukin-34 orchestrates bone formation through its binding to bone morphogenic proteins.Theranostics · 2025Article
- TREM2Frontiers in immunology · 2025Review
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bone marrow microenvironment supports leukocyte mobilization and differentiation and controls the development of leukemias, including acute myeloid leukemia (AML). Here, we found that the development of AML xenotransplants was suppressed in mice with osteoclasts tuberous sclerosis 1 (Tsc1) deletion. Tsc1-deficient osteoclasts released a high level of interleukin-34 (IL-34), which efficiently induced AML cell differentiation and prevented AML progression in various preclinical models. Conversely, AML development was accelerated in mice deficient in IL-34. Interestingly, IL-34 inhibited AML independent of its known receptors but bound directly to triggering receptor expressed on myeloid cells 2 (TREM2), a key hub of immune signals. TREM2-deficient AML cells and normal myeloid cells were resistant to IL-34 treatment. Mechanistically, IL-34-TREM2 binding rapidly phosphorylated Ras protein activator like 3 and inactivated extracellular signal-regulated protein kinase 1/2 signaling to prevent AML cell proliferation and stimulate differentiation. Furthermore, TREM2 was downregulated in patients with AML and associated with a poor prognosis. This study identified TREM2 as a novel receptor for IL-34, indicating a promising strategy for overcoming AML differentiation blockade in patients with AML.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.