ArticleCancer discovery2022
Unleashing Cell-Intrinsic Inflammation as a Strategy to Kill AML Blasts.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
36 citing papers in PubMed, 48 citations in OpenAlex.
- Azacitidine, Venetoclax, and Magrolimab in Newly Diagnosed and Relapsed Refractory Acute Myeloid Leukemia: Phase Ib/II Study and Correlative Analysis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Article
- Inhibition of p300/CREBBP catalytic activity drives context-dependent transcriptional activation in AML.Blood · 2026Article
- Elevated levels of TNF and its targets characterize better-risk older acute myeloid leukemia patients.Leukemia · 2026Article
- Article
- Patients with AML with WT TP53 but defective TP53-mediated apoptosis have a dismal survival.JCI insight · 2026Article
- Article
- Scaffolding-dependent CASP1 constrains excessive cell-intrinsic inflammatory signaling in leukemia.Cell chemical biology · 2026Article
- Article
- A 3'UTR polymorphism disrupts IRF2BP2 autoregulation through an eIF4H translational enhancer.Frontiers in genetics · 2026Article
- Characterization of Chemoresistant Cell Populations Improves Risk Stratification and Therapy Prediction in Pediatric AML.bioRxiv : the preprint server for biology · 2025Article
- Multi-selective RAS(ON) Inhibition Targets Oncogenic RAS Mutations and Overcomes RAS/MAPK-Mediated Resistance to FLT3 and BCL2 Inhibitors in Acute Myeloid Leukemia.bioRxiv : the preprint server for biology · 2025Article
- Therapeutic hurdles in acute myeloid leukemia: Leukemic stem cells, inflammation and immune dysfunction.Current opinion in pharmacology · 2025Review
- Inflammatory signaling pathways play a role in SYK inhibitor resistant AML.Scientific reports · 2025Article
- Pbx3-mediated suppression of type I interferon response contributes to leukemia progression driven by MLL-AF9.Cancer gene therapy · 2025Article
- Acute resistance to BET inhibitors remodels compensatory transcriptional programs via p300 coactivation.Blood · 2025Article
- Innate immune-inflammatory signaling milieu in myeloid leukemia and aging-associated clonal hematopoiesis pathologies.Frontiers in immunology · 2025Review
- Immunosuppressive cells in acute myeloid leukemia: mechanisms and therapeutic target.Frontiers in immunology · 2025Review
- Super-Enhancer-Driven IRF2BP2 is Activated by Master Transcription Factors and Sustains T-ALL Cell Growth and Survival.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Malate initiates a proton-sensing pathway essential for pH regulation of inflammation.Signal transduction and targeted therapy · 2024Article
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Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
Abstract
Leukemic blasts are immune cells gone awry. We hypothesized that dysregulation of inflammatory pathways contributes to the maintenance of their leukemic state and can be exploited as cell-intrinsic, self-directed immunotherapy. To this end, we applied genome-wide screens to discover genetic vulnerabilities in acute myeloid leukemia (AML) cells implicated in inflammatory pathways. We identified the immune modulator IRF2BP2 as a selective AML dependency. We validated AML cell dependency on IRF2BP2 with genetic and protein degradation approaches in vitro and genetically in vivo. Chromatin and global gene-expression studies demonstrated that IRF2BP2 represses IL1β/TNFα signaling via NFκB, and IRF2BP2 perturbation results in an acute inflammatory state leading to AML cell death. These findings elucidate a hitherto unexplored AML dependency, reveal cell-intrinsic inflammatory signaling as a mechanism priming leukemic blasts for regulated cell death, and establish IRF2BP2-mediated transcriptional repression as a mechanism for blast survival. SIGNIFICANCE: This study exploits inflammatory programs inherent to AML blasts to identify genetic vulnerabilities in this disease. In doing so, we determined that AML cells are dependent on the transcriptional repressive activity of IRF2BP2 for their survival, revealing cell-intrinsic inflammation as a mechanism priming leukemic blasts for regulated cell death. See related commentary by Puissant and Medyouf, p. 1617. This article is highlighted in the In This Issue feature, p. 1599.
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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 OpenQuestion graph.