ArticleProceedings of the National Academy of Sciences of the United States of America2018
NOXA genetic amplification or pharmacologic induction primes lymphoma cells to BCL2 inhibitor-induced cell death.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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
33 citing papers in PubMed, 50 citations in OpenAlex.
- The BH3-only protein NOXA is essential for apoptosis induction by BH3-mimetics targeting BCL2 or BCL-XBritish journal of haematology · 2026Article
- Multifaceted Roles of Bcl-2 Family Proteins: Regulatory Roles in Apoptosis, Physiological Functions, and Therapeutic Potential.Current medical science · 2025Review
- BCL-2 dependence is a favorable predictive marker of response to therapy for chronic lymphocytic leukemia.Molecular cancer · 2025Article
- Article
- Review
- Quantitative systems pharmacology modeling of tumor heterogeneity in response to BH3-mimetics using virtual tumors calibrated with cell viability assays.CPT: pharmacometrics & systems pharmacology · 2024Article
- PMAIP1 promotes J subgroup avian leukosis virus replication by regulating mitochondrial function.Poultry science · 2024Article
- Targeting regulated cell death pathways in cancers for effective treatment: a comprehensive review.Frontiers in cell and developmental biology · 2024Review
- β-Sitosterol Suppresses Lipopolysaccharide-Induced Inflammation and Lipogenesis Disorder in Bovine Mammary Epithelial Cells.International journal of molecular sciences · 2023Article
- Molecular classification and therapeutics in diffuse large B-cell lymphoma.Frontiers in molecular biosciences · 2023Review
- TP53 mutations and RNA-binding protein MUSASHI-2 drive resistance to PRMT5-targeted therapy in B-cell lymphoma.Nature communications · 2022Article
- The Pt(International journal of molecular sciences · 2022Article
- The paradigm of drug resistance in cancer: an epigenetic perspective.Bioscience reports · 2022Review
- Identification of NOXA as a pivotal regulator of resistance to CAR T-cell therapy in B-cell malignancies.Signal transduction and targeted therapy · 2022Article
- Synergistic activity of combined inhibition of anti-apoptotic molecules in B-cell precursor ALL.Leukemia · 2022Article
- Anti-apoptotic MCL1 Protein Represents Critical Survival Molecule for Most Burkitt Lymphomas and BCL2-negative Diffuse Large B-cell Lymphomas.Molecular cancer therapeutics · 2022Article
- Tumor-targeted nanoparticles improve the therapeutic index of BCL2 and MCL1 dual inhibition.Blood · 2021Article
- Article
- Molecular Genetics of Relapsed Diffuse Large B-Cell Lymphoma: Insight into Mechanisms of Therapy Resistance.Cancers · 2020Review
- BH3 Mimetics for the Treatment of B-Cell Malignancies-Insights and Lessons from the Clinic.Cancers · 2020Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Although diffuse large B cell lymphoma (DLBCL) cells widely express the BCL2 protein, they rarely respond to treatment with BCL2-selective inhibitors. Here we show that DLBCL cells harboring PMAIP1/NOXA gene amplification were highly sensitive to BCL2 small-molecule inhibitors. In these cells, BCL2 inhibition induced cell death by activating caspase 9, which was further amplified by caspase-dependent cleavage and depletion of MCL1. In DLBCL cells lacking NOXA amplification, BCL2 inhibition was associated with an increase in MCL1 protein abundance in a BIM-dependent manner, causing a decreased antilymphoma efficacy. In these cells, dual inhibition of MCL1 and BCL2 was required for enhanced killing. Pharmacologic induction of NOXA, using the histone deacetylase inhibitor panobinostat, decreased MCL1 protein abundance and increased lymphoma cell vulnerability to BCL2 inhibitors in vitro and in vivo. Our data provide a mechanistic rationale for combination strategies to disrupt lymphoma cell codependency on BCL2 and MCL1 proteins in DLBCL.
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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.