ArticleBlood cancer journal2015
Loss in MCL-1 function sensitizes non-Hodgkin's lymphoma cell lines to the BCL-2-selective inhibitor venetoclax (ABT-199).
Article in Blood cancer journal, 2015. 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 66 papers.
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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.
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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
66 citing papers in PubMed, 113 citations in OpenAlex.
- Hybrid dosing of the cyclin-dependent kinase (CDK) inhibitor flavopiridol in relapsed/refractory mantle cell lymphoma and diffuse large B-cell lymphoma.Leukemia & lymphoma · 2019Trial
- Targeted Penetrating Motif Engineering of BH3 Mimetic: Harnessing Non-Canonical Amino Acids for Coinhibition of MCL-1 and BCL-xL in Acute Myeloid Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pioneering the Battle Against Breast Cancer: The Promise of New Bcl-2 Family.Anti-cancer agents in medicinal chemistry · 2025Review
- Potent combination benefit of the AKT inhibitor capivasertib and the BCL-2 inhibitor venetoclax in diffuse large B cell lymphoma.Leukemia · 2024Article
- A Phase 1 First-in-Human Study of the MCL-1 Inhibitor AZD5991 in Patients with Relapsed/Refractory Hematologic Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- 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
- Identifying Targetable Vulnerabilities to Circumvent or Overcome Venetoclax Resistance in Diffuse Large B-Cell Lymphoma.Cancers · 2024Article
- Myeloid Targeted Human MLL-ENL and MLL-AF9 Induces cdk9 and bcl2 Expression in Zebrafish Embryos.PLoS genetics · 2024Article
- KS18, a Mcl-1 inhibitor, improves the effectiveness of bortezomib and overcomes resistance in refractory multiple myeloma by triggering intrinsic apoptosis.Frontiers in pharmacology · 2024Article
- Article
- Glutathione promotes the synergistic effects of venetoclax and azacytidine against myelodysplastic syndrome‑refractory anemia by regulating the cell cycle.Experimental and therapeutic medicine · 2023Article
- AMG176, an MCL-1 inhibitor, is active in pre-clinical models of aggressive B-cell lymphomas.Leukemia & lymphoma · 2023Article
- Sensitivity of canine hematological cancers to BH3 mimetics.Journal of veterinary internal medicine · 2023Article
- Review
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Discovery, development and application of drugs targeting BCL-2 pro-survival proteins in cancer.Biochemical Society transactions · 2021Review
- Balancing Properties with Carboxylates: A Lead Optimization Campaign for Selective and Orally Active CDK9 Inhibitors.ACS medicinal chemistry letters · 2021Article
- Targeting Bfl-1 via acute CDK9 inhibition overcomes intrinsic BH3-mimetic resistance in lymphomas.Blood · 2021Article
- Review
- Targeting MCL-1 in cancer: current status and perspectives.Journal of hematology & oncology · 2021Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a population, non-Hodgkin's lymphoma (NHL) cell lines positive for the t(14;18) translocation and/or possessing elevated BCL2 copy number (CN; BCL2(High)) are exquisitely sensitive to navitoclax or the B-cell lymphoma protein-2 (BCL-2)-selective inhibitor venetoclax. Despite this, some BCL2(High) cell lines remain resistant to either agent. Here we show that the MCL-1-specific inhibitor A-1210477 sensitizes these cell lines to navitoclax. Chemical segregation of this synergy with the BCL-2-selective inhibitor venetoclax or BCL-XL-selective inhibitor A-1155463 indicated that MCL-1 and BCL-2 are the two key anti-apoptotic targets for sensitization. Similarly, the CDK inhibitor flavopiridol downregulated MCL-1 expression and synergized with venetoclax in BCL2(High) NHL cell lines to a similar extent as A-1210477. A-1210477 also synergized with navitoclax in the majority of BCL2(Low) NHL cell lines. However, chemical segregation with venetoclax or A-1155463 revealed that synergy was driven by BCL-XL inhibition in this population. Collectively these data emphasize that BCL2 status is predictive of venetoclax potency in NHL not only as a single agent, but also in the adjuvant setting with anti-tumorigenic agents that inhibit MCL-1 function. These studies also potentially identify a patient population (BCL2(Low)) that could benefit from BCL-XL (navitoclax)-driven combination therapy.
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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.