ArticleBlood2001
Apo2L/TRAIL and Bcl-2-related proteins regulate type I interferon-induced apoptosis in multiple myeloma.
Article in Blood, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 201 citations in OpenAlex.
- Timing-Dependent Immunostimulatory Activity of Human IFN-β mRNA in Primary Human Myeloid Cells.Vaccines · 2026Article
- AAV immuno-gene therapy platform delivering vectorized cytokines defines a new modality for high-grade glioma treatment.Molecular therapy. Oncology · 2026Article
- Context-dependent impact of type I interferon signaling in cancer.Molecular cancer · 2025Review
- Multiple mechanisms contribute to acquired TRAIL resistance in multiple myeloma.Cancer cell international · 2024Article
- Mitochondria-associated programmed cell death: elucidating prognostic biomarkers, immune checkpoints, and therapeutic avenues in multiple myeloma.Frontiers in immunology · 2024Article
- Targeting telomeres: advances in telomere maintenance mechanism-specific cancer therapies.Nature reviews. Cancer · 2022Review
- A Three-Gene Signature Predicts Response to Selinexor in Multiple Myeloma.JCO precision oncology · 2022Article
- The gamble between oncolytic virus therapy and IFN.Frontiers in immunology · 2022Review
- Interferon α2-Thymosin α1 Fusion Protein (IFNα2-Tα1): A Genetically Engineered Fusion Protein with Enhanced Anticancer and Antiviral Effect.Materials (Basel, Switzerland) · 2021Article
- ISG12a and its interaction partner NR4A1 are involved in TRAIL-induced apoptosis in hepatoma cells.Journal of cellular and molecular medicine · 2019Article
- Function of HNRNPC in breast cancer cells by controlling the dsRNA-induced interferon response.The EMBO journal · 2018Article
- New variant identified in major susceptibility locus to tuberculosis on chromosomal region 8q12-q13 in Moroccan population: a case control study.BMC infectious diseases · 2017Article
- Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy.Oncotarget · 2017Review
- PU.1 acts as tumor suppressor for myeloma cells through direct transcriptional repression of IRF4.Oncogene · 2017Article
- Overexpression of RKIP and its cross-talk with several regulatory gene products in multiple myeloma.Journal of experimental & clinical cancer research : CR · 2017Review
- Mcl-1 signals pathway inhibitors in mouse peritoneal macrophage apoptosis infected with the Xinjiang strain ofInternational journal of clinical and experimental pathology · 2017Article
- Lipopolysaccharide (LPS) Promotes Apoptosis in Human Breast Epithelial × Breast Cancer Hybrids, but Not in Parental Cells.PloS one · 2016Article
- Down-regulation of HMGB1 expression by shRNA constructs inhibits the bioactivity of urothelial carcinoma cell lines via the NF-κB pathway.Scientific reports · 2015Article
- Helper T lymphocyte response in the peripheral blood of patients with intraepithelial neoplasia submitted to immunotherapy with pegylated interferon-α.International journal of molecular sciences · 2015Article
- Threonine 32 (Thr32) of FoxO3 is critical for TGF-β-induced apoptosis via Bim in hepatocarcinoma cells.Protein & cell · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
It has been reported that interferons (IFNs) may have antitumor activity in multiple myeloma (MM). The mechanism for their effect on MM, however, remains elusive. This study shows that IFN-alpha and -beta, but not -gamma, induce apoptosis characterized by Annexin V positivity, nuclear fragmentation and condensation, and loss of clonogenicity in 3 MM cell lines (U266, RPMI-8266, and NCI-H929), and in plasma cells from 10 patients with MM. Apo2 ligand (Apo2L, also TRAIL) induction was one of the earliest events following IFN administration in U266 cells. Treatment of these cells with TRAIL, but not with Fas agonistic antibodies, induces apoptosis. Cell death induced by IFNs and Apo2L in U266 cells was partially blocked by a dominant-negative Apo2L receptor, DR5, demonstrating the functional significance of Apo2L induction. This study shows that IFNs activate caspases and the mitochondrial-dependent apoptotic pathway, possibly mediated by Apo2L production. Thus, IFN-alpha and -beta induce cytochrome c release from mitochondria starting at 12 hours, with an amplified release seen at 48 hours. Moreover, Bid cleavage precedes the initial cytochrome c release, whereas the late, amplified cytochrome c release coincides with changes in levels of Bcl-2, Bcl-X(L), and reduction of mitochondrial membrane potential. These results link the Apo2L induction and modulation of Bcl-2 family proteins to mitochondrial dysfunction. Furthermore, IFNs and Apo2L induce cell death of CD38(+)/CD45(-/dim) plasma cells, without significant effect on nonplasma blood cells, in a caspase and Bcl-2 cleavage-dependent manner. These results warrant further clinical studies with IFNs and Apo2L in MM.
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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.