Trial reportBritish journal of haematology2011
Bortezomib interacts synergistically with belinostat in human acute myeloid leukaemia and acute lymphoblastic leukaemia cells in association with perturbations in NF-κB and Bim.
Trial report in British journal of haematology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Meta-analysis of incidence and risk of peripheral neuropathy associated with intravenous bortezomib.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2015Pooled it
- The anticancer effect of the HDAC inhibitor belinostat is enhanced by inhibitors of Bcl-xMolecular oncology · 2025Article
- Decoding NF-κB: nucleocytoplasmic shuttling dynamics, synthetic modulation and post-therapeutic behavior in cancer.Molecular biology reports · 2025Review
- Synthesis of fluorinated tubastatin A derivatives with bi-, tri-, and tetracyclic cap groups: molecular docking with HDAC6 and evaluation ofRSC medicinal chemistry · 2025Article
- Epigenetic Regulation and Therapeutic Targeting of Alternative Splicing Dysregulation in Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Identification and validation of a novel prognostic model based on anoikis‑related genes in acute myeloid leukemia.Oncology letters · 2025Article
- Multi-Omic Analysis Reveals the Impact of Bortezomib in Hyperleukocytic Acute Myeloid Leukemia.Cancer medicine · 2024Article
- Current treatment strategies targeting histone deacetylase inhibitors in acute lymphocytic leukemia: a systematic review.Frontiers in oncology · 2024Review
- Bortezomib Is Effective in the Treatment of T Lymphoblastic Leukaemia by Inducing DNA Damage, WEE1 Downregulation, and Mitotic Catastrophe.International journal of molecular sciences · 2023Article
- Anti-multiple myeloma potential of resynthesized belinostat derivatives: an experimental study on cytotoxic activity, drug combination, and docking studies.RSC advances · 2022Article
- NF-κB: A Druggable Target in Acute Myeloid Leukemia.Cancers · 2022Review
- Dual-Targeted Therapy Circumvents Non-Genetic Drug Resistance to Targeted Therapy.Frontiers in oncology · 2022Review
- Phase 1 study of belinostat (PXD-101) and bortezomib (Velcade, PS-341) in patients with relapsed or refractory acute leukemia and myelodysplastic syndrome.Leukemia & lymphoma · 2021Article
- Antibody-drug nanoparticle induces synergistic treatment efficacies in HER2 positive breast cancer cells.Scientific reports · 2021Article
- Inhibition of autophagy enhances apoptosis induced by bortezomib in AML cells.Oncology letters · 2021Article
- The Role of HDAC6 in Autophagy and NLRP3 Inflammasome.Frontiers in immunology · 2021Review
- Role of HDACs in normal and malignant hematopoiesis.Molecular cancer · 2020Review
- HDAC Inhibitors in Acute Myeloid Leukemia.Cancers · 2019Review
- Histone deacetylase 6 in cancer.Journal of hematology & oncology · 2018Review
- Cancer Drug Response Profile scan (CDRscan): A Deep Learning Model That Predicts Drug Effectiveness from Cancer Genomic Signature.Scientific reports · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Interactions between the histone deacetylase inhibitor belinostat and the proteasome inhibitor bortezomib were investigated in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) cells. Co-administration of sub-micromolar concentrations of belinostat with low nanomolar concentrations of bortezomib sharply increased apoptosis in both AML and ALL cell lines and primary blasts. Synergistic interactions were associated with interruption of both canonical and non-canonical nuclear factor (NF)-κB signalling pathways, e.g. accumulation of the phosphorylated (S32/S36) form of IκBα, diminished belinostat-mediated RelA/p65 hyperacetylation (K310), and reduced processing of p100 into p52. These events were accompanied by down-regulation of NF-κB-dependent pro-survival proteins (e.g. XIAP, Bcl-xL). Moreover, belinostat/bortezomib co-exposure induced up-regulation of the BH3-only pro-death protein Bim. Significantly, shRNA knock-down of Bim substantially reduced the lethality of belinostat/bortezomib regimens. Administration of belinostat ± bortezomib also induced hyperacetylation (K40) of α-tubulin, indicating histone deacetylase inhibitor 6 inhibition. Finally, in contrast to the pronounced lethality of belinostat/bortezomib toward primary leukaemia blasts, equivalent treatment was relatively non-toxic to normal CD34(+) cells. Together, these findings indicate that belinostat and bortezomib interact synergistically in both cultured and primary AML and ALL cells, and raise the possibilities that up-regulation of Bim and interference with NF-κB pathways contribute to this phenomenon. They also suggest that combined belinostat/bortezomib regimens warrant further attention in acute leukaemias.
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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.