ArticleLeukemia2016
Rationale and efficacy of proteasome inhibitor combined with arsenic trioxide in the treatment of acute promyelocytic leukemia.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 36 citations in OpenAlex.
- A phase II study evaluating the role of bortezomib in the management of relapsed acute promyelocytic leukemia treated upfront with arsenic trioxide.Cancer medicine · 2020Trial
- Synergistic Molecular Strategies for Targeting the Unfolded Protein Response in Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The autophagy switch: A critical determinant of arsenic-induced carcinogenesis and cancer therapy.Toxicology reports · 2026Review
- Venetoclax induces mitochondrial apoptosis and autophagy to overcome arsenic trioxide resistance in acute promyelocytic leukemia.Journal of translational medicine · 2026Article
- Stroma-driven horizontal transfer of TCA-related proteins mediates metabolic plasticity and imatinib resistance in chronic myeloid leukemia.Cell communication and signaling : CCS · 2025Article
- Ubiquitination regulates autophagy in cancer: simple modifications, promising targets.Journal of translational medicine · 2024Review
- Ablation of Wnt signaling in bone marrow stromal cells overcomes microenvironment-mediated drug resistance in acute myeloid leukemia.Scientific reports · 2024Article
- 1,3-Benzodioxole Derivatives Improve the Anti-Tumor Efficiency of Arsenicals.International journal of molecular sciences · 2022Article
- Mitochondrial metabolism as a target for acute myeloid leukemia treatment.Cancer & metabolism · 2021Review
- Evolving Chemotherapy Free Regimens for Acute Promyelocytic Leukemia.Frontiers in oncology · 2021Review
- Resource utilization and cost effectiveness of treating acute promyelocytic leukaemia using generic arsenic trioxide.British journal of haematology · 2020Article
- Combination Lenalidomide/Bortezomib Treatment Synergistically Induces Calpain-Dependent Ikaros Cleavage and Apoptosis in Myeloma Cells.Molecular cancer research : MCR · 2020Article
- Review
- Pyrrolidine Dithiocarbamate Facilitates Arsenic Trioxide Against Pancreatic Cancer via Perturbing Ubiquitin-Proteasome Pathway.Cancer management and research · 2020Article
- Acute Promyelocytic Leukemia: Update on the Mechanisms of Leukemogenesis, Resistance and on Innovative Treatment Strategies.Cancers · 2019Review
- Stromal cells downregulate miR-23a-5p to activate protective autophagy in acute myeloid leukemia.Cell death & disease · 2019Article
- Autophagy: New Insights into Mechanisms of Action and Resistance of Treatment in Acute Promyelocytic leukemia.International journal of molecular sciences · 2019Review
- Review
- A personalized approach to acute myeloid leukemia therapy: current options.Pharmacogenomics and personalized medicine · 2019Article
- Retinoic acid and arsenic trioxide sensitize acute promyelocytic leukemia cells to ER stress.Leukemia · 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
17 authors at 2 institutions in 2 countries.
Funding
Abstract
Arsenic trioxide (ATO) mediates PML-RARA (promyelocytic leukemia-retinoic acid receptor-α) oncoprotein degradation via the proteasome pathway and this degradation appears to be critical for achieving cure in acute promyeloytic leukemia (APL). We have previously demonstrated significant micro-environment-mediated drug resistance (EMDR) to ATO in APL. Here we demonstrate that this EMDR could be effectively overcome by combining a proteasome inhibitor (bortezomib) with ATO. A synergistic effect on combining these two agents in vitro was noted in both ATO-sensitive and ATO-resistant APL cell lines. The mechanism of this synergy involved downregulation of the nuclear factor-κB pathway, increase in unfolded protein response (UPR) and an increase in reactive oxygen species generation in the malignant cell. We also noted that PML-RARA oncoprotein is effectively cleared with this combination in spite of proteasome inhibition by bortezomib, and that this clearance is mediated through a p62-dependent autophagy pathway. We further demonstrated that proteasome inhibition along with ATO had an additive effect in inducing autophagy. The beneficial effect of this combination was further validated in an animal model and in an on-going clinical trial. This study raises the potential of a non-myelotoxic proteasome inhibitor replacing anthracyclines in the management of high-risk and relapsed APL.
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.