ArticleBlood advances2018
Activation of MYC, a bona fide client of HSP90, contributes to intrinsic ibrutinib resistance in mantle cell lymphoma.
Article in Blood advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 60 citations in OpenAlex.
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- Trial
- Coordinated regulation of the metaboproteome by Hsp90 chaperones controls metabolic plasticity.iScience · 2026Article
- Mechanisms of resistance to BTK inhibitors in B cell malignancies and emerging targeted strategies.Molecular therapy. Oncology · 2026Review
- Acquired MYC rearrangement potentially associated with ibrutinib resistance in mantle cell lymphoma.Virchows Archiv : an international journal of pathology · 2026Article
- Cyclin-Dependent Kinase-9 and Oxidative Phosphorylation Inhibition Overcomes Ibrutinib Resistance in Mantle Cell Lymphoma.Cancer research communications · 2026Article
- Zanubrutinib-based regimen as the salvage or bridging treatment of CART therapy in relapsed or refractory, non-germinal center B-cell-like diffuse large B-cell lymphoma: a retrospective multicenter cohort study.Frontiers in immunology · 2026Observational
- B-cell receptor signaling and microenvironment crosstalk in mantle cell lymphoma.Cell communication and signaling : CCS · 2025Review
- Targeting proteostasis pathways for cancer therapy.Journal of pharmaceutical analysis · 2025Review
- MYC protein is a high-risk factor in mantle cell lymphoma and identifies cases beyond morphology, proliferation andHaematologica · 2024Article
- Targeting lysine demethylase 5 (KDM5) in mantle cell lymphoma.Blood cancer journal · 2024Article
- The HSP90-MYC-CDK9 network drives therapeutic resistance in mantle cell lymphoma.Experimental hematology & oncology · 2024Article
- Potentiation of apoptosis in drug-resistant mantle cell lymphoma cells by MCL-1 inhibitor involves downregulation of inhibitor of apoptosis proteins.Cell death & disease · 2023Article
- SIRT1 and HSP90α feed-forward circuit safeguards chromosome segregation integrity in diffuse large B cell lymphomas.Cell death & disease · 2023Article
- 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 factor 1 (HSF1) specifically potentiates c-MYC-mediated transcription independently of the canonical heat shock response.Cell reports · 2023Article
- HSPs/STAT3 Interplay Sustains DDR and Promotes Cytokine Release by Primary Effusion Lymphoma Cells.International journal of molecular sciences · 2023Article
- Heat-Shock Proteins in Leukemia and Lymphoma: Multitargets for Innovative Therapeutic Approaches.Cancers · 2023Review
- Resistance to Bruton tyrosine kinase inhibition in chronic lymphocytic leukaemia and non-Hodgkin lymphoma.British journal of haematology · 2023Review
- NRF2 in Cancer: Cross-Talk with Oncogenic Pathways and Involvement in Gammaherpesvirus-Driven Carcinogenesis.International journal of molecular sciences · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The BTK inhibitor ibrutinib has demonstrated a remarkable therapeutic effect in mantle cell lymphoma (MCL). However, approximately one-third of patients do not respond to the drug initially. To identify the mechanisms underlying primary ibrutinib resistance in MCL, we analyzed the transcriptome changes in ibrutinib-sensitive and ibrutinib-resistant cell lines on ibrutinib treatment. We found that MYC gene signature was suppressed by ibrutinib in sensitive but not resistant cell lines. We demonstrated that MYC gene was structurally abnormal and MYC protein was overexpressed in MCL cells. Further, MYC knockdown with RNA interference inhibited cell growth in ibrutinib-sensitive as well as ibrutinib-resistant cells. We explored the possibility of inhibiting MYC through HSP90 inhibition. The chaperon protein is overexpressed in both cell lines and primary MCL cells from the patients. We demonstrated that MYC is a bona fide client of HSP90 in the context of MCL by both immunoprecipitation and chemical precipitation. Furthermore, inhibition of HSP90 using PU-H71 induced apoptosis and caused cell cycle arrest. PU-H71 also demonstrates strong and relatively specific inhibition of the MYC transcriptional program compared with other oncogenic pathways. In a MCL patient-derived xenograft model, the HSP90 inhibitor retards tumor growth and prolongs survival. Last, we showed that PU-H71 induced apoptosis and downregulated MYC protein in MCL cells derived from patients who were clinically resistant to ibrutinib. In conclusion, MYC activity underlies intrinsic resistance to ibrutinib in MCL. As a client protein of HSP90, MYC can be inhibited via PU-H71 to overcome primary ibrutinib resistance.
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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.