ArticleOncogene2002
Mechanisms of resistance to TRAIL-induced apoptosis in primary B cell chronic lymphocytic leukaemia.
Article in Oncogene, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 195 citations in OpenAlex.
- Genetic association between TRAIL-R1 Thr209Arg and cancer susceptibility.Scientific reports · 2015Pooled it
- In-silico identification of genetic variants associated with chronic lymphocytic leukemia for diagnostic and therapeutic applications.Scientific reports · 2026Article
- EX527, a sirtuins 1 inhibitor, sensitizes T-cell leukemia to death receptor-mediated apoptosis by downregulating cellular FLICE inhibitory protein.Cancer biology & therapy · 2024Article
- Review
- The Identification of New c-FLIP Inhibitors for Restoring Apoptosis in TRAIL-Resistant Cancer Cells.Current issues in molecular biology · 2024Article
- Targeted PI3K/AKT-hyperactivation induces cell death in chronic lymphocytic leukemia.Nature communications · 2021Article
- Article
- Genetic variations in tumor ecrosis factor related apoptosis-inducing ligand receptor-1 (TRAIL-R1) gene and the susceptibility to b-cell non-hodgkin lymphoma (B-NHL) in Egypt.Cancer biomarkers : section A of Disease markers · 2021Article
- Targeting apoptotic caspases in cancer.Biochimica et biophysica acta. Molecular cell research · 2020Review
- The fungal metabolite chaetocin is a sensitizer for pro-apoptotic therapies in glioblastoma.Cell death & disease · 2019Article
- Sensitization of recombinant human tumor necrosis factor-related apoptosis-inducing ligand-resistant malignant melanomas by quercetin.Melanoma research · 2018Article
- Article
- Pevonedistat, a Nedd8-activating enzyme inhibitor, sensitizes neoplastic B-cells to death receptor-mediated apoptosis.Oncotarget · 2017Article
- Identification of Novel Epitopes with Agonistic Activity for the Development of Tumor Immunotherapy Targeting TRAIL-R1.Journal of Cancer · 2017Article
- Temozolomide sensitizes stem-like cells of glioma spheres to TRAIL-induced apoptosis via upregulation of casitas B-lineage lymphoma (c-Cbl) protein.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Recombinant human CD19L-sTRAIL effectively targets B cell precursor acute lymphoblastic leukemia.The Journal of clinical investigation · 2015Article
- Glucose--a sweet way to die: metabolic switching modulates tumor cell death.Cell cycle (Georgetown, Tex.) · 2012Article
- The transcription factor Wilms tumor 1 confers resistance in myeloid leukemia cells against the proapoptotic therapeutic agent TRAIL (tumor necrosis factor α-related apoptosis-inducing ligand) by regulating the antiapoptotic protein Bcl-xL.The Journal of biological chemistry · 2012Article
- A death effector domain chain DISC model reveals a crucial role for caspase-8 chain assembly in mediating apoptotic cell death.Molecular cell · 2012Article
- Tumor necrosis factor (TNF) receptor-associated factor 7 is required for TNFα-induced Jun NH2-terminal kinase activation and promotes cell death by regulating polyubiquitination and lysosomal degradation of c-FLIP protein.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary B cells from B cell chronic lymphocytic leukaemia (B-CLL) were resistant to the novel selective cytotoxic agent, TNF-related apoptosis-inducing ligand (TRAIL). Low levels of the death-inducing TRAIL receptors, TRAIL-R1 and TRAIL-R2 but not the putative 'decoy' receptors, TRAIL-R3 and TRAIL-R4, were expressed on the surface of B-CLL cells. Resistance to TRAIL was upstream of caspase-8 activation, as little or no caspase-8 was processed in TRAIL-treated B-CLL cells. Low levels of a TRAIL death-inducing signalling complex (DISC) were formed in these cells, accompanied by the recruitment of endogenous FADD, caspase-8 and c-FLIP(L) but not c-FLIP(S). Both caspase-8 and c-FLIP(L) were cleaved to form two stable intermediates of approximately 43 kDa, which remained associated with the DISC. Caspase-8 was not further processed to its active heterotetramer. Thus the resistance of B-CLL cells to TRAIL may be due partly to low surface expression of the death receptors resulting in low levels of DISC formation and also to the high ratio of c-FLIP(L) to caspase-8 within the DISC, which would prevent further activation of caspase-8. Our results highlight the possibility of sensitising B-CLL cells to TRAIL by modulation of c-FLIP levels or by upregulation of surface expression of death receptors.
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