ArticleHaematologica2021
The IL1-IL1RAP axis plays an important role in the inflammatory leukemic niche that favors acute myeloid leukemia proliferation over normal hematopoiesis
Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- The proteomic architecture of clonal hematopoiesis: a systematic review of niche remodeling and multi-compartment predictors of malignant transformation.Frontiers in medicine · 2026Pooled it
- Severe inflammation and lineage skewing are associated with poor engraftment of engineered hematopoietic stem cells in patients with sickle cell disease.Nature communications · 2025Trial
- Inflammation as a central driver in AML pathogenesis and therapy resistance.Science China. Life sciences · 2026Review
- Isocitrate dehydrogenase 1 mutations drive downregulation of IL1R1 and dysregulated inflammatory response in acute myeloid leukemia.Blood cancer journal · 2026Article
- Anakinra for tocilizumab-refractory febrile infection-related epilepsy syndrome with normal IL-1β levels: a case report.Frontiers in immunology · 2026Article
- IL-1 signaling and inflammasomes in acute myeloid leukemia: mechanisms and therapeutic opportunities.Cellular and molecular life sciences : CMLS · 2025Review
- Demystifying the diagnosis and management of ICUS, CHIP, and CCUS.Hematology. American Society of Hematology. Education Program · 2025Review
- Dual targeting of tumoral cells and immune microenvironment by blocking the IL-33/IL1RL1 pathway.Nature communications · 2025Article
- Galectin-9 induces IL-1β production as a key inflammatory cytokine in the acute myeloid leukemia cell line (U937).Research in pharmaceutical sciences · 2025Article
- C-FOS promotes the formation of neutrophil extracellular traps and the recruitment of neutrophils in lung metastasis of triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Goat Milk Protein-Derived ACE Inhibitory Peptide SLPQ Exerts Hypertension Alleviation Effects Partially by Regulating the Inflammatory Stress of Endothelial Cells.Foods (Basel, Switzerland) · 2024Article
- Autophagy and inflammasome activation are associated with poor response to FLT3 inhibitors in patients with FLT3-ITD acute myeloid leukemia.Scientific reports · 2024Article
- Obesity modulates hematopoietic stem cell fate decision via IL-1β induced p38/MAPK signaling pathway.Stem cell research & therapy · 2024Article
- IL1RAP-specific T cell engager depletes acute myeloid leukemia stem cells.Journal of hematology & oncology · 2024Article
- Bone marrow inflammation in haematological malignancies.Nature reviews. Immunology · 2024Review
- The Bone Marrow Immune Microenvironment in CML: Treatment Responses, Treatment-Free Remission, and Therapeutic Vulnerabilities.Current hematologic malignancy reports · 2023Review
- Insights Regarding the Role of Inflammasomes in Leukemia: What Do We Know?Journal of immunology research · 2023Review
- Chimeric antigen receptor T-cells targeting IL-1RAP: a promising new cellular immunotherapy to treat acute myeloid leukemia.Journal for immunotherapy of cancer · 2022Article
- Toll-like Receptor 4, Osteoblasts and Leukemogenesis; the Lesson from Acute Myeloid Leukemia.Molecules (Basel, Switzerland) · 2022Review
- The cytokine network in acute myeloid leukemia.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upregulation of the plasma membrane receptor IL1RAP in Acute Myeloid Leukemia (AML) has been reported but its role in the context of the leukemic bone marrow niche is unclear. Here, we studied the signaling events downstream of IL1RAP in relation to leukemogenesis and normal hematopoiesis. High IL1RAP expression was associated with a leukemic GMP-like state, and knockdown of IL1RAP in AML reduced colony-forming capacity. Stimulation with IL1β resulted in the induction of multiple chemokines and an inflammatory secretome via the p38 MAPK and NFκB signaling pathways in IL1RAP-expressing AML cells, but IL1β-induced signaling was dispensable for AML cell proliferation and NFκB-driven survival. IL1RAP was also expressed in stromal cells where IL1β induced expression of inflammatory chemokines and cytokines as well. Intriguingly, the IL1β-induced inflammatory secretome of IL1RAPexpressing AML cells grown on a stromal layer of mesenchymal stem cells affected normal hematopoiesis including hematopoietic stem/progenitor cells while AML cell proliferation was not affected. The addition of Anakinra, an FDA-approved IL1 receptor antagonist, could reverse this effect. Therefore, blocking the IL1-IL1RAP signaling axis might be a good therapeutic approach to reduce inflammation in the bone marrow niche and thereby promote normal hematopoietic recovery over AML proliferation after chemotherapy.
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Registered trials
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