ArticleBlood advances2020
BET inhibitors synergize with venetoclax to induce apoptosis in MYC-driven lymphomas with high BCL-2 expression.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 47 citations in OpenAlex.
- The ETS-family transcription factor PU.1 is a critical regulator of the inhibitory Fcγ receptor IIB expression in humans.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- BET inhibition revealed varying MYC dependency mechanisms independent of gene alterations in aggressive B-cell lymphomas.Clinical epigenetics · 2024Article
- Targeted BET inhibition with OPN-51107 synergizes with venetoclax in chronic lymphocytic leukemia.Leukemia & lymphoma · 2024Article
- Bromodomain proteins as potential therapeutic targets for B-cell non-Hodgkin lymphoma.Cell & bioscience · 2024Review
- Inhibition of bromodomain and extra-terminal proteins targets constitutively active NFκB and STAT signaling in lymphoma and influences the expression of the antiapoptotic proteins BCL2A1 and c-MYC.Cell communication and signaling : CCS · 2024Article
- Targeted inhibition of DHODH is synergistic with BCL2 blockade in HGBCL with concurrent MYC and BCL2 rearrangement.BMC cancer · 2024Article
- BET inhibition reforms the immune microenvironment and alleviates T cell dysfunction in chronic lymphocytic leukemia.JCI insight · 2024Article
- Super enhancer lncRNAs: a novel hallmark in cancer.Cell communication and signaling : CCS · 2024Review
- Super-enhancers and the super-enhancer reader BRD4: tumorigenic factors and therapeutic targets.Cell death discovery · 2023Review
- BET in hematologic tumors: Immunity, pathogenesis, clinical trials and drug combinations.Genes & diseases · 2023Review
- The Epigenetic Reader, Bromodomain Containing 2, Mediates Cholangiocyte Senescence via Interaction With ETS Proto-Oncogene 1.Gastroenterology · 2023Article
- Impact of Histone Modifications and Their Therapeutic Targeting in Hematological Malignancies.International journal of molecular sciences · 2022Review
- Article
- Altered pathways and targeted therapy in double hit lymphoma.Journal of hematology & oncology · 2022Review
- The manipulation of apoptosis for cancer therapy using BH3-mimetic drugs.Nature reviews. Cancer · 2022Review
- Dual inhibition of BET and HAT/p300 suppresses colorectal cancer via DR5- and p53/PUMA-mediated cell death.Frontiers in oncology · 2022Article
- Histone Modifications and Their Targeting in Lymphoid Malignancies.International journal of molecular sciences · 2021Review
- BET Proteins as Attractive Targets for Cancer Therapeutics.International journal of molecular sciences · 2021Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Although the MYC oncogenic network represents an attractive therapeutic target for lymphoma, MYC inhibitors have been difficult to develop. Alternatively, inhibitors of epigenetic/ transcriptional regulators, particularly the bromodomain and extraterminal (BET) family, have been used to modulate MYC. However, current benzodiazepine-derivative BET inhibitors (BETi) elicit disappointing responses and dose-limiting toxicity in relapsed/refractory lymphoma, potentially because of enrichment of high-risk molecular features and chemical backbone-associated toxicities. Consequently, novel nonbenzodiazepine BETi and improved mechanistic understanding are required. Here we characterize the responses of aggressive MYC-driven lymphomas to 2 nonbenzodiazepine BETi: PLX51107 and PLX2853. Both invoked BIM-dependent apoptosis and in vivo therapy, associated with miR-17∼92 repression, in murine Eµ-myc lymphomas, with PLX2853 exhibiting enhanced potency. Accordingly, exogenous BCL-2 expression abrogated these effects. Because high BCL-2 expression is common in diffuse large B-cell lymphoma (DLBCL), BETi were ineffective in driving apoptosis and in vivo therapy of DLBCL cell lines, mirroring clinical results. However, BETi-mediated BIM upregulation and miR-17∼92 repression remained intact. Consequently, coadministration of BETi and ABT199/venetoclax restored cell death and in vivo therapy. Collectively, these data identify BIM-dependent apoptosis as a critical mechanism of action for this class of BETi that, via coadministration of BH3 mimetics, can deliver effective tumor control in DLBCL.
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.