ArticleCell communication and signaling : CCS2024
Targeting NLRP3 inhibits AML progression by inducing PERK/eIF2-mediated apoptosis.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Cell surface GRP78 and the UPR pathway as novel promising therapeutic targets in cancer: an insight into the treatment of acute leukemia by using GRP78-CART cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- IL-1 signaling and inflammasomes in acute myeloid leukemia: mechanisms and therapeutic opportunities.Cellular and molecular life sciences : CMLS · 2025Review
- Mesenchymal stem cell-derived exosomes ameliorate gentamicin-induced vestibular hair cell injury by regulating the SNARE pathway and enhancing autophagy.Stem cell research & therapy · 2025Article
- Integrative multi-omic analysis of NLRP3 inflammasome dysregulation and subtyping for personalized treatment in acute myeloid leukemia.Discover oncology · 2025Article
- Inhibition of NLRP3 enhances pro-apoptotic effects of FLT3 inhibition in AML.Cell communication and signaling : CCS · 2025Article
- Current Knowledge of the Integrated Stress Response in the Development and Management of Acute Myeloid Leukemia: A Novel Target with Encouraging Progress.Drug design, development and therapy · 2025Review
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Authors and funding
30 authors.
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Abstract
backgroundAcute myeloid leukemia (AML) is characterized by the abnormal proliferation of myeloid precursor cells and presents significant challenges in treatment due to its heterogeneity. Recently, the NLRP3 inflammasome has emerged as a potential contributor to AML pathogenesis, although its precise mechanisms remain poorly understood.
methodsPublic genome datasets were utilized to evaluate the expression of NLRP3 inflammasome-related genes (IL-1β, IL-18, ASC, and NLRP3) in AML patients compared to healthy individuals. CRISPR/Cas9 technology was employed to generate NLRP3-deficient MOLM-13 AML cells, followed by comprehensive characterization using real-time PCR, western blotting, FACS analysis, and transmission electron and immunofluorescence microscopy. Proteomic analyses were conducted to identify NLRP3-dependent alterations in protein levels, with a focus on the eIF2 kinase PERK-mediated signaling pathways. Additionally, in vivo studies were performed using a leukemic mouse model to elucidate the pathogenic role of NLRP3 in AML.
resultsElevated expression of NLRP3 was significantly associated with diminished overall survival in AML patients. Genetic deletion, pharmacological inhibition and silencing by RNA interference of NLRP3 led to decreased AML cell survival through the induction of apoptosis. Proteomic analyses uncovered NLRP3-dependent alterations in protein translation, characterized by enhanced eIF2α phosphorylation in NLRP3-deficient AML cells. Moreover, inhibition of PERK-mediated eIF2α phosphorylation reduced apoptosis by downregulating pro-apoptotic Bcl-2 family members. In vivo studies demonstrated reduced leukemic burden in mice engrafted with NLRP3 knockout AML cells, as evidenced by alleviated leukemic symptoms.
conclusionOur findings elucidate the involvement of the NLRP3/PERK/eIF2 axis as a novel driver of AML cell survival. Targeting NLRP3-induced signaling pathways, particularly through the PERK/eIF2 axis, presents a promising therapeutic strategy for AML intervention. These insights into the role of the NLRP3 inflammasome offer potential avenues for improving the prognosis and treatment outcomes of AML patients.
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