Trial reportBlood2011
Bortezomib resistance in mantle cell lymphoma is associated with plasmacytic differentiation.
Trial report in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00131976, which is not on this map. Cited by 66 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Who cites it
66 citing papers in PubMed, 117 citations in OpenAlex.
- Early relapse after single auto-SCT for multiple myeloma is a major predictor of survival in the era of novel agents.Bone marrow transplantation · 2015Trial
- Trial
- Multifunctional CD38 in the pathogenesis and treatment of B-cell lymphomas.American journal of blood research · 2026Review
- A new era in cancer therapy: targeting the Proteasome-Bcl-2 axis.Journal of experimental & clinical cancer research : CR · 2025Review
- Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.Clinical and experimental medicine · 2025Review
- Role of TRIM24 in the regulation of proteasome-autophagy crosstalk in bortezomib-resistant mantle cell lymphoma.Cell death discovery · 2025Article
- Dihydrolipoamide dehydrogenase (DLD) is a novel molecular target of bortezomib.Cell death & disease · 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
- Advancements in B-Cell Non-Hodgkin's Lymphoma: From Signaling Pathways to Targeted Therapies.Advances in hematology · 2024Review
- Empowering macrophages: the cancer fighters within the tumour microenvironment in mantle cell lymphoma.Frontiers in immunology · 2024Review
- Targeted inhibition of protein synthesis renders cancer cells vulnerable to apoptosis by unfolded protein response.Cell death & disease · 2023Article
- Beyond Bruton's tyrosine kinase inhibitors in mantle cell lymphoma: bispecific antibodies, antibody-drug conjugates, CAR T-cells, and novel agents.Journal of hematology & oncology · 2023Review
- The mitochondrial pyruvate carrier complex potentiates the efficacy of proteasome inhibitors in multiple myeloma.Blood advances · 2023Article
- Compromised antigen binding and signaling interfere with bispecific CD19 and CD79a chimeric antigen receptor function.Blood advances · 2023Article
- PAX5 aberrant expression incorporated in MIPI-SP risk scoring system exhibits additive value in mantle cell lymphoma.Journal of molecular medicine (Berlin, Germany) · 2023Article
- A Machine Learning Model to Predict Survival and Therapeutic Responses in Multiple Myeloma.International journal of molecular sciences · 2023Article
- BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications.Molecules (Basel, Switzerland) · 2023Review
- Metabolomics: A New Era in the Diagnosis or Prognosis of B-Cell Non-Hodgkin's Lymphoma.Diagnostics (Basel, Switzerland) · 2023Review
- Bcl-2 Family Members Bcl-xL and Bax Cooperatively Contribute to Bortezomib Resistance in Mantle Cell Lymphoma.International journal of molecular sciences · 2022Article
- Molecular Determinants Underlying the Anti-Cancer Efficacy of CD38 Monoclonal Antibodies in Hematological Malignancies.Biomolecules · 2022Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
Bortezomib induces remissions in 30%-50% of patients with relapsed mantle cell lymphoma (MCL). Conversely, more than half of patients' tumors are intrinsically resistant to bortezomib. The molecular mechanism of resistance has not been defined. We generated a model of bortezomib-adapted subclones of the MCL cell lines JEKO and HBL2 that were 40- to 80-fold less sensitive to bortezomib than the parental cells. Acquisition of bortezomib resistance was gradual and reversible. Bortezomib-adapted subclones showed increased proteasome activity and tolerated lower proteasome capacity than the parental lines. Using gene expression profiling, we discovered that bortezomib resistance was associated with plasmacytic differentiation, including up-regulation of IRF4 and CD38 and expression of CD138. In contrast to plasma cells, plasmacytic MCL cells did not increase immunoglobulin secretion. Intrinsically bortezomib-resistant MCL cell lines and primary tumor cells from MCL patients with inferior clinical response to bortezomib also expressed plasmacytic features. Knockdown of IRF4 was toxic for the subset of MCL cells with plasmacytic differentiation, but only slightly sensitized cells to bortezomib. We conclude that plasmacytic differentiation in the absence of an increased secretory load can enable cells to withstand the stress of proteasome inhibition. Expression of CD38 and IRF4 could serve as markers of bortezomib resistance in MCL. This study has been registered at http://clinicaltrials.gov as NCT00131976.
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What OpenQuestion holds
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.