ArticleThe Journal of clinical investigation2014
Positive feedback between NF-κB and TNF-α promotes leukemia-initiating cell capacity.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers.
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Who cites it
144 citing papers in PubMed, 216 citations in OpenAlex.
- A Phase 2 study of bortezomib combined with either idarubicin/cytarabine or cytarabine/etoposide in children with relapsed, refractory or secondary acute myeloid leukemia: a report from the Children's Oncology Group.Pediatric blood & cancer · 2014Trial
- Inflammation as a central driver in AML pathogenesis and therapy resistance.Science China. Life sciences · 2026Review
- Modulation of nociceptive nerve activity as a novel therapeutic strategy in acute myeloid leukemia.Fundamental research · 2026Article
- Article
- Discovery of BEND4 as a novel single-gene prognostic marker and therapeutic target for adverse AML.NPJ precision oncology · 2026Article
- L arginine and radiofrequency electromagnetic field attenuate inflammatory and apoptotic injury after experimental subarachnoid hemorrhage.Scientific reports · 2026Article
- Refined detection of CD34⁺CD38⁻CD45RA⁺ leukemic stem cells using a single-tube flow cytometry assay and its strong association with measurable residual disease in acute myeloid leukemia: a retrospective cohort study.Stem cell research & therapy · 2026Article
- Amygdalin synergizes with the TNF-α monoclonal antibody infliximab to modulate HSP90 and related necro-inflammatory/oxidative stress pathways in a rat model of hepatic I/R.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- High Expression of GPR183 Predicts Poor Survival in Cytogenetically Normal Acute Myeloid Leukemia.Biochemical genetics · 2026Article
- Leukemia-driven expansion of type 3 innate lymphoid cell facilitates a pro-tumoral microenvironment in acute myeloid leukemia.Leukemia · 2026Article
- CYLD Limits Neutrophil-Driven Psoriatic Inflammation.Inflammation · 2026Article
- T cell acute lymphoblastic leukemia exploits a neural proinflammatory pathway to colonize the meninges.The Journal of clinical investigation · 2026Article
- The tumor microenvironment as a key regulator of radiotherapy response.Frontiers in immunology · 2026Review
- Targeting the nuclear factor kappa B pathway for the medical management of intervertebral disc degeneration.Frontiers in neuroscience · 2026Review
- The GPR183-oxysterol axis in cancer: immune trafficking, spatial organization, and therapeutic potential.Frontiers in immunology · 2026Review
- Abnormal Homeostasis in the Redox State and Related Signaling Pathways, in Irritable Bowel Syndrome.Neurogastroenterology and motility · 2025Article
- Brazilein Impedes IKK Activation by Disrupting RIPK1 Polyubiquitination, Increasing Apoptotic Susceptibility in Cells with Constitutively Active NF-κB.Biomolecules & therapeutics · 2025Article
- Review
- JAK-STAT-activated, fratricide-resistant CAR-T cells targeting membrane-bound TNF effectively treat AML and solid tumors.Journal for immunotherapy of cancer · 2025Article
- Unraveling the Role of Microcystin-LR in Ferroptosis and Sepsis Pathogenesis: A Comprehensive Review.Biomolecules · 2025Review
84 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy that originates from leukemia-initiating cells (LICs). The identification of common mechanisms underlying LIC development will be important in establishing broadly effective therapeutics for AML. Constitutive NF-κB pathway activation has been reported in different types of AML; however, the mechanism of NF-κB activation and its importance in leukemia progression are poorly understood. Here, we analyzed myeloid leukemia mouse models to assess NF-κB activity in AML LICs. We found that LICs, but not normal hematopoietic stem cells or non-LIC fractions within leukemia cells, exhibited constitutive NF-κB activity. This activity was maintained through autocrine TNF-α secretion, which formed an NF-κB/TNF-α positive feedback loop. LICs had increased levels of active proteasome machinery, which promoted the degradation of IκBα and further supported NF-κB activity. Pharmacological inhibition of the proteasome complex markedly suppressed leukemia progression in vivo. Conversely, enhanced activation of NF-κB signaling expanded LIC frequency within leukemia cell populations. We also demonstrated a strong correlation between NF-κB activity and TNF-α secretion in human AML samples. Our findings indicate that NF-κB/TNF-α signaling in LICs contributes to leukemia progression and provide a widely applicable approach for targeting LICs.
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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.