ArticleOncotarget2015
Inhibition of Lyn is a promising treatment for mantle cell lymphoma with bortezomib resistance.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- RETRACTED: Kim et al. Inhibition of EphA2 by Dasatinib Suppresses Radiation-Induced Intestinal Injury.International journal of molecular sciences · 2026Article
- Targeting SET to counteract Lyn activation demonstrates anti-cancer potential in diffuse large B-cell lymphoma.Clinical and experimental medicine · 2025Article
- B-Cell Receptor Signaling and Beyond: The Role of Igα (CD79a)/Igβ (CD79b) in Normal and Malignant B Cells.International journal of molecular sciences · 2023Review
- Bcl-2 Family Members Bcl-xL and Bax Cooperatively Contribute to Bortezomib Resistance in Mantle Cell Lymphoma.International journal of molecular sciences · 2022Article
- Article
- Review
- Lyn Kinase Promotes the Proliferation of Malignant Melanoma Cells through Inhibition of Apoptosis and Autophagy via the PI3K/Akt Signaling Pathway.Journal of Cancer · 2019Article
- Combining a QSAR Approach and Structural Analysis to Derive an SAR Map of Lyn Kinase Inhibition.Molecules (Basel, Switzerland) · 2018Article
- Mesenchymal stem cell-mediated Notch2 activation overcomes radiation-induced injury of the hematopoietic system.Scientific reports · 2018Article
- Development of expression-based biomarkers of Dasatinib response in hematologic malignancies.Blood cancer journal · 2017Article
- Tyrosine kinase inhibitor therapy-induced changes in humoral immunity in patients with chronic myeloid leukemia.Journal of cancer research and clinical oncology · 2017Article
- The preclinical discovery and development of bortezomib for the treatment of mantle cell lymphoma.Expert opinion on drug discovery · 2017Review
- Bruton tyrosine kinase inhibitor ONO/GS-4059: from bench to bedside.Oncotarget · 2017Review
- BIRC6 mediates imatinib resistance independently of Mcl-1.PloS one · 2017Article
- Bortezomib-resistance is associated with increased levels of proteasome subunits and apoptosis-avoidance.Oncotarget · 2016Article
- Targeting B-cell receptor signaling in leukemia and lymphoma: how and why?International journal of hematologic oncology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although proteasome inhibition with bortezomib (BTZ) is a validated treatment for relapsed or refractory mantle cell lymphoma (MCL), many patients show resistance to BTZ. However, the molecular mechanism of BTZ resistance in MCL has not been elucidated. In the present study, we investigated BTZ-resistant MCL cells in vitro and in vivo. We demonstrate that BTZ-resistant MCL cells showed highly increased expression of the B-cell receptor (BCR) components CD79A and CD19. Activation of the BCR signaling pathway enhanced the activity of Src family kinases (SFKs), especially Lyn, and downstream kinases PI3K/AKT/mTOR in BTZ-resistant MCL cells. Depletion of CD79A and Lyn significantly reduced several kinase activities involved in PI3K signaling, leading to inhibition of proliferation. In addition, the SFKs inhibitor dasatinib inhibited the proliferation of BTZ-resistant cells, preventing the binding of CD19 with Lyn and PI3K p85. We also verified our findings with the mouse xenograft tumor model. Dasatinib treatment significantly decreased tumor size in the mouse bearing BTZ-resistant MCL cells, but not in the mouse bearing BTZ-sensitive MCL cells. Collectively, our data show that overexpression of the BCR and its activated signaling confers BTZ resistance in MCL cells. Thus, targeting BCR signaling with dasatinib could be a novel therapeutic approach for patients with MCL that has relapsed or is refractory to treatment with BTZ.
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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.