ArticleLeukemia2016
BET inhibition represses miR17-92 to drive BIM-initiated apoptosis of normal and transformed hematopoietic cells.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 36 citations in OpenAlex.
- Overcoming BET-inhibitor JQ1 resistance in aggressive non-small cell lung cancer by inducing ferroptosis via inhibition of the BRD2-FTH1 axis.The FEBS journal · 2025Article
- BRD4 inhibition leads to MDSC apoptosis and enhances checkpoint blockade therapy.The Journal of clinical investigation · 2025Article
- Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Regulation of programmed cell death by Brd4.Cell death & disease · 2022Review
- Review
- Co-Operativity between MYC and BCL-2 Pro-Survival Proteins in Cancer.International journal of molecular sciences · 2021Review
- BRD4-mediated repression of p53 is a target for combination therapy in AML.Nature communications · 2021Article
- BET inhibitors synergize with venetoclax to induce apoptosis in MYC-driven lymphomas with high BCL-2 expression.Blood advances · 2020Article
- miR17~92 restrains pro-apoptotic BIM to ensure survival of haematopoietic stem and progenitor cells.Cell death and differentiation · 2020Article
- Ferritinophagy is required for the induction of ferroptosis by the bromodomain protein BRD4 inhibitor (+)-JQ1 in cancer cells.Cell death & disease · 2019Article
- Combined venetoclax and alvocidib in acute myeloid leukemia.Oncotarget · 2017Article
- Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond.Molecular carcinogenesis · 2017Review
- Targeting BET proteins improves the therapeutic efficacy of BCL-2 inhibition in T-cell acute lymphoblastic leukemia.Leukemia · 2017Article
- Inhibition of BET bromodomain-dependent XIAP and FLIP expression sensitizes KRAS-mutated NSCLC to pro-apoptotic agents.Cell death & disease · 2016Article
- Anticancer bioactive peptide-3 inhibits human gastric cancer growth by targeting miR-338-5p.Cell & bioscience · 2016Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The BET (bromodomain and extraterminal domain) bromodomain-containing proteins, such as BRD4, are highly promising targets for treating lymphoid and myeloid malignancies. They act to modulate the expression of multiple genes that control diverse cellular processes including proliferation, survival and differentiation that are consequentially disrupted by small-molecule BET bromodomain inhibitors such as JQ1. By assessing the impact of these inhibitors on normal mouse hematopoietic cells or their transformed counterparts, we establish definitively that their cytotoxic action in vitro and in vivo relies predominantly on the activation of BAX/BAK-dependent mitochondrial (intrinsic) apoptosis. In large part, this is triggered by marked upregulation of the BH3-only protein BIM when the BET inhibitors suppress miR-17-92, a key post-transcriptional repressor of BIM expression. Thus, our study strongly suggests that mutations that permit the evasion of apoptosis (for example, BCL2 overexpression, BIM inactivation) are likely to blunt the activity of the BET bromodomain inhibitors and should be anticipated when therapy resistance develops. Strikingly, we also found that certain normal hematopoietic cells, especially those of lymphoid origin, are as prone to apoptosis induced by the BET inhibitors as their transformed counterparts, indicating that their susceptibility to BET inhibitors did not arise from oncogenic transformation.
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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.