ArticleBlood2017
HSP90 promotes Burkitt lymphoma cell survival by maintaining tonic B-cell receptor signaling.
Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Lymphoma and Leukemia Cell Vulnerabilities and Resistance Identified by Compound Library Screens.Methods in molecular biology (Clifton, N.J.) · 2025Article
- SH2 domain-containing inositol 5-phosphatases support the survival of Burkitt lymphoma cells by promoting energy metabolism.Haematologica · 2024Article
- Cytokine-Induced Killer Cells in Combination with Heat Shock Protein 90 Inhibitors Functioning via the Fas/FasL Axis Provides Rationale for a Potential Clinical Benefit in Burkitt's lymphoma.International journal of molecular sciences · 2023Article
- Heat-Shock Proteins in Leukemia and Lymphoma: Multitargets for Innovative Therapeutic Approaches.Cancers · 2023Review
- Heat shock protein 90 is a new potential target of anti-rejection therapy in allotransplantation.Cell stress & chaperones · 2022Article
- Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer.Biomolecules · 2022Review
- Heat Shock Proteins in Lymphoma Immunotherapy.Frontiers in immunology · 2021Review
- Post-translational modifications of Hsp90 and translating the chaperone code.The Journal of biological chemistry · 2020Review
- Burkitt lymphoma: bridging the gap between advances in molecular biology and therapy.Leukemia & lymphoma · 2020Review
- Inhibition of HSP90 overcomes melphalan resistance through downregulation of Src in multiple myeloma cells.Clinical and experimental medicine · 2020Article
- Article
- Drug-based perturbation screen uncovers synergistic drug combinations in Burkitt lymphoma.Scientific reports · 2018Article
- Drug-perturbation-based stratification of blood cancer.The Journal of clinical investigation · 2018Article
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Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
Abstract
Burkitt lymphoma (BL) is an aggressive B-cell neoplasm that is currently treated by intensive chemotherapy in combination with anti-CD20 antibodies. Because of their toxicity, current treatment regimens are often not suitable for elderly patients or for patients in developing countries where BL is endemic. Targeted therapies for BL are therefore needed. In this study, we performed a compound screen in 17 BL cell lines to identify small molecule inhibitors affecting cell survival. We found that inhibitors of heat shock protein 90 (HSP90) induced apoptosis in BL cells in vitro at concentrations that did not affect normal B cells. By global proteomic and phosphoproteomic profiling, we show that, in BL, HSP90 inhibition compromises the activity of the pivotal B-cell antigen receptor (BCR)-proximal effector spleen tyrosine kinase (SYK), which we identified as an HSP90 client protein. Consistently, expression of constitutively active TEL-SYK counteracted the apoptotic effect of HSP90 inhibition. Together, our results demonstrate that HSP90 inhibition impairs BL cell survival by interfering with tonic BCR signaling, thus providing a molecular rationale for the use of HSP90 inhibitors in the treatment of BL.
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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.