ArticleBritish journal of haematology2013
The Bruton tyrosine kinase (BTK) inhibitor PCI-32765 synergistically increases proteasome inhibitor activity in diffuse large-B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells sensitive or resistant to bortezomib.
Article in British journal of haematology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 41 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.
The trial behind it
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
41 citing papers in PubMed, 84 citations in OpenAlex.
- The Prognostic Impact of Dose-attenuated R-CHOP Therapy for Elderly Patients with Diffuse Large B-cell Lymphoma.Internal medicine (Tokyo, Japan) · 2018Trial
- Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib.Haematologica · 2015Trial
- Inhibition of proteolytic and ATPase activities of the proteasome by the BTK inhibitor CGI-1746.iScience · 2024Article
- Interplay between proteasome inhibitors and NF-κB pathway in leukemia and lymphoma: a comprehensive review on challenges ahead of proteasome inhibitors.Cell communication and signaling : CCS · 2024Review
- Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: a phase 1/2 trial of the European MCL network (SAKK 36/13).EClinicalMedicine · 2023Article
- DLBCL 1L-What to Expect beyond R-CHOP?Cancers · 2022Review
- Regulation of B-Cell Receptor Signaling and Its Therapeutic Relevance in Aggressive B-Cell Lymphomas.Cancers · 2022Review
- Why R-CHOP + X is not enough: lessons learned and next steps in the mission to improve frontline therapy for diffuse large B-cell lymphoma.Leukemia & lymphoma · 2021Article
- Article
- Review
- A Deep Insight Into CAR-T Cell Therapy in Non-Hodgkin Lymphoma: Application, Opportunities, and Future Directions.Frontiers in immunology · 2021Review
- A Phase I/II first-line study of R-CHOP plus B-cell receptor/NF-κB-double-targeting to molecularly assess therapy response.International journal of hematologic oncology · 2019Article
- Bortezomib for the Treatment of Hematologic Malignancies: 15 Years Later.Drugs in R&D · 2019Review
- Inhibition of the PI3K/AKT signaling pathway sensitizes diffuse large B-cell lymphoma cells to treatment with proteasome inhibitors via suppression of BAG3.Oncology letters · 2019Article
- Combination of Enzastaurin and Ibrutinib synergistically induces anti-tumor effects in diffuse large B cell lymphoma.Journal of experimental & clinical cancer research : CR · 2019Article
- BTK suppresses myeloma cellular senescence through activating AKT/P27/Rb signaling.Oncotarget · 2017Article
- MicroRNA-26a/cyclin-dependent kinase 5 axis controls proliferation, apoptosis and in vivo tumor growth of diffuse large B-cell lymphoma cell lines.Cell death & disease · 2017Article
- Comparative genomic expression signatures of signal transduction pathways and targets in paediatric Burkitt lymphoma: a Children's Oncology Group report.British journal of haematology · 2017Article
- Molecular Subtyping in Diffuse Large B Cell Lymphoma: Closer to an Approach of Precision Therapy.Current treatment options in oncology · 2017Review
- Ibrutinib in Waldenström macroglobulinemia: latest evidence and clinical experience.Therapeutic advances in hematology · 2016Review
Corrections and comments
- Correction · 2019-02-18Duplication of/in Image · Falsification/Fabrication of Image · Investigation by Company/Institution · Investigation by ORI · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · · Girija Dasmahapatra has an ORI finding of research misconduct;
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- Erratum issuedCorrigendum.2019
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Interactions between the Bruton tyrosine kinase (BTK) inhibitor PCI-32765 and the proteasome inhibitor (bortezomib) were examined in diffuse large-B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells, including those highly resistant to bortezomib. Co-administration of PCI-32765/bortezomib synergistically increased mitochondrial injury and apoptosis in germinal centre- or activated B-cell-like-DLBCL cells and in MCL cells. These events were accompanied by marked AKT and nuclear factor (NF)-κB (NFKB1) inactivation, down-regulation of Mcl-1 (MCL1), Bcl-xL (BCL2L1), and XIAP, and enhanced DNA damage (e.g., γH2A.X formation) and endoplasmic reticulum (ER) stress. Similar interactions were observed in highly bortezomib-resistant DLBCL and MCL cells, and in primary DLBCL cells. In contrast, PCI-32765/bortezomib regimens displayed minimal toxicity toward normal CD34(+) bone marrow cells. Transfection of DLBCL cells with a constitutively active AKT construct attenuated AKT inactivation and significantly diminished cell death, whereas expression of an NF-κB "super-repressor" (IκBαser34/36 ) increased both PCI-32765 and bortezomib lethality. Moreover, cells in which the ER stress response was disabled by a dominant-negative eIF2α construct were resistant to this regimen. Finally, combined exposure to PCI-32765 and bortezomib resulted in more pronounced and sustained reactive oxygen species (ROS) generation, and ROS scavengers significantly diminished lethality. Given promising early clinical results for PCI-32765 in DLBCL and MCL, a strategy combining BTK/proteasome inhibitor warrants attention in these malignancies.
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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.