ArticleBlood cancer journal2019
Superior efficacy of cotreatment with BET protein inhibitor and BCL2 or MCL1 inhibitor against AML blast progenitor cells.
Article in Blood cancer journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Targeting AraC-Resistant Acute Myeloid Leukemia by Dual Inhibition of CDK9 and Bcl-2: A Systematic Review and Meta-Analysis.Journal of healthcare engineering · 2022Pooled it
- Bromodomain-Driven Regulation of Stem Cells: A Potential Target for Cancer Therapeutic Intervention.Stem cell reviews and reports · 2026Review
- Src inhibition potentiates MCL-1 antagonist activity in acute myeloid leukemia.Signal transduction and targeted therapy · 2025Article
- NL101 synergizes with the BCL-2 inhibitor venetoclax through PI3K-dependent suppression of c-Myc in acute myeloid leukaemia.Journal of translational medicine · 2024Article
- A Review of the Bromodomain and Extraterminal Domain Epigenetic Reader Proteins: Function on Virus Infection and Cancer.Viruses · 2024Review
- Therapeutic Potential of Bromodomain and Extra-Terminal Domain Inhibitors for Synovial Sarcoma Cells.Cancers · 2024Article
- Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM).Blood cancer journal · 2024Article
- Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.Signal transduction and targeted therapy · 2023Review
- Combination of a New Oral Demethylating Agent, OR2100, and Venetoclax for Treatment of Acute Myeloid Leukemia.Cancer research communications · 2023Article
- Epigenetic targeting to enhance acute myeloid leukemia-directed immunotherapy.Frontiers in immunology · 2023Review
- Targeting MCL-1 protein to treat cancer: opportunities and challenges.Frontiers in oncology · 2023Review
- Article
- Article
- Increased MCL-1 synthesis promotes irradiation-induced nasopharyngeal carcinoma radioresistance via regulation of the ROS/AKT loop.Cell death & disease · 2022Article
- Efficacy of CDK9 inhibition in therapy of post-myeloproliferative neoplasm (MPN) secondary (s) AML cells.Blood cancer journal · 2022Article
- Effective Menin inhibitor-based combinations against AML with MLL rearrangement or NPM1 mutation (NPM1c).Blood cancer journal · 2022Article
- Can the Gene Expression Profile of Patients with Acute Myeloid Leukemia Predict Complete Remission Following Induction Therapy?Journal of Cancer · 2022Article
- Inhibition of the anti-apoptotic protein MCL-1 severely suppresses human hematopoiesisHaematologica · 2021Article
- Article
- 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
20 authors at 3 institutions in 1 country.
Funding
Abstract
First-generation bromodomain extra-terminal protein (BETP) inhibitors (BETi) (e.g., OTX015) that disrupt binding of BETP BRD4 to chromatin transcriptionally attenuate AML-relevant progrowth and prosurvival oncoproteins. BETi treatment induces apoptosis of AML BPCs, reduces in vivo AML burden and induces clinical remissions in a minority of AML patients. Clinical efficacy of more potent BETis, e.g., ABBV-075 (AbbVie, Inc.), is being evaluated. Venetoclax and A-1210477 bind and inhibit the antiapoptotic activity of BCL2 and MCL1, respectively, lowering the threshold for apoptosis. BETi treatment is shown here to perturb accessible chromatin and activity of enhancers/promoters, attenuating MYC, CDK6, MCL1 and BCL2, while inducing BIM, HEXIM1, CDKN1A expressions and apoptosis of AML cells. Treatment with venetoclax increased MCL1 protein levels, but cotreatment with ABBV-075 reduced MCL1 and Bcl-xL levels. ABBV-075 cotreatment synergistically induced apoptosis with venetoclax or A-1210477 in patient-derived, CD34+ AML cells. Compared to treatment with either agent alone, cotreatment with ABBV-075 and venetoclax was significantly more effective in reducing AML cell-burden and improving survival, without inducing toxicity, in AML-engrafted immune-depleted mice. These findings highlight the basis of superior activity and support interrogation of clinical efficacy and safety of cotreatment with BETi and BCL2 or MCL1 inhibitor in AML.
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.