ArticleLeukemia2019
Transient stabilization, rather than inhibition, of MYC amplifies extrinsic apoptosis and therapeutic responses in refractory B-cell lymphoma.
Article in Leukemia, 2019. 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 17 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Potential therapeutic GSK-3β inhibitor 9-ING-41 is active in combination with venetoclax in double-hit lymphoma (DHL).Cancer biology & therapy · 2025Article
- Targeting the TRIB3-MYC axis in cancer: mechanistic insights and therapeutic disruption strategies.Investigational new drugs · 2025Review
- Article
- Combination drug screen identifies synergistic drug interaction of BCL-XL and class I histone deacetylase inhibitors in MYC-amplified medulloblastoma cells.Journal of neuro-oncology · 2024Article
- A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors.Communications biology · 2023Article
- Review
- Elraglusib (formerly 9-ING-41) possesses potent anti-lymphoma properties which cannot be attributed to GSK3 inhibition.Cell communication and signaling : CCS · 2023Article
- FBXW7β isoform drives transcriptional activation of the proinflammatory TNF cluster in human pro-B cells.Blood advances · 2023Article
- The Helix-Loop-Helix motif of human EIF3A regulates translation of proliferative cellular mRNAs.PloS one · 2023Article
- mTOR inhibition attenuates chemosensitivity through the induction of chemotherapy resistant persisters.Nature communications · 2022Article
- The Tumor Suppressor Protein TRAF3 Modulates GSK3 Activity and Susceptibility of B Lymphoma Cells to GSK3 Inhibition.Cancers · 2022Article
- Review
- MYC Hyperactivates Wnt Signaling inMolecular cancer research : MCR · 2021Article
- Tilting MYC toward cancer cell death.Trends in cancer · 2021Review
- Alternative approaches to target Myc for cancer treatment.Signal transduction and targeted therapy · 2021Review
- Lithium and Therapeutic Targeting of GSK-3.Cells · 2021Review
- "Double-Hit" Chronic Lymphocytic Leukemia, Involving theFrontiers in oncology · 2021Review
Corrections and comments
- Erratum issuedCorrection: Transient stabilization, rather than inhibition, of MYC amplifies extrinsic apoptosis and therapeutic responses in refractory B-cell lymphoma.2020 · Klein, Peter [corrected to Klein, Peter S]
Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
Therapeutic targeting of initiating oncogenes is the mainstay of precision medicine. Considerable efforts have been expended toward silencing MYC, which drives many human cancers including Burkitt lymphomas (BL). Yet, the effects of MYC silencing on standard-of-care therapies are poorly understood. Here we found that inhibition of MYC transcription renders B-lymphoblastoid cells refractory to chemotherapeutic agents. This suggested that in the context of chemotherapy, stabilization of Myc protein could be more beneficial than its inactivation. We tested this hypothesis by pharmacologically inhibiting glycogen synthase kinase 3β (GSK-3β), which normally targets Myc for proteasomal degradation. We discovered that chemorefractory BL cell lines responded better to doxorubicin and other anti-cancer drugs when Myc was transiently stabilized. In vivo, GSK3 inhibitors (GSK3i) enhanced doxorubicin-induced apoptosis in BL patient-derived xenografts (BL-PDX), as well as in murine MYC-driven lymphoma allografts. This enhancement was accompanied by and required deregulation of several key genes acting in the extrinsic, death-receptor-mediated apoptotic pathway. Consistent with this mechanism of action, GSK3i also facilitated lymphoma cell killing by a death ligand TRAIL and by a death receptor agonist mapatumumab. Thus, GSK3i synergizes with both standard chemotherapeutics and direct engagers of death receptors and could improve outcomes in patients with refractory lymphomas.
Indexed as
Identifiers
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.