ArticleScientific reports2021
Activity of immunoproteasome inhibitor ONX-0914 in acute lymphoblastic leukemia expressing MLL-AF4 fusion protein.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- Carfilzomib plus induction chemotherapy for children with relapsed or refractory acute lymphoblastic leukemia.Blood advances · 2026Trial
- Protein Posttranslational Modifications in Immunity: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- ONX-0914 Alleviates Impaired Diabetic Wound Healing by Restoring Redox Homeostasis and Modulating Pro-Inflammatory Response.Medicina (Kaunas, Lithuania) · 2026Article
- ONX-0914 Suppresses Hormone-Sensitive Prostate Cancer by Promoting O-GlcNAcylation-Mediated Stabilization of TCF7L1.Oncology research · 2026Article
- Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures.Cancer cell · 2025Article
- Highly specific Immunoproteasome inhibitor M3258 induces proteotoxic stress and apoptosis in KMT2A::AFF1 driven acute lymphoblastic leukemia.Scientific reports · 2025Article
- Ubiquitin-conjugating enzyme UBE2N modulates proteostasis in immunoproteasome-positive acute myeloid leukemia.The Journal of clinical investigation · 2025Article
- Recent Advances in the Development of Immunoproteasome Inhibitors as Anti-Cancer Agents: The Past 5 Years.Molecules (Basel, Switzerland) · 2025Review
- From oncogenesis to prognosis: the roles of the immunoproteasome in cancer.Frontiers in immunology · 2025Review
- Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia.Cancer medicine · 2024Review
- The role of proteasomes in tumorigenesis.Genes & diseases · 2024Review
- Interplay between proteasome inhibitors and NF-κB pathway in leukemia and lymphoma: a comprehensive review on challenges ahead of proteasome inhibitors.Cell communication and signaling : CCS · 2024Review
- Enhancing the immunogenicity of Wilms tumor 1 epitope in mesothelioma cells with immunoproteasome inhibitors.PloS one · 2024Article
- Probiotic lactic acid bacteria promote anti-tumor immunity through enhanced major histocompatibility complex class I-restricted antigen presentation machinery in dendritic cells.Frontiers in immunology · 2024Article
- Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia.Molecular cancer · 2023Article
- Therapeutic approaches for HTLV-1-associated adult T-cell leukemia/lymphoma: a comprehensive review.Medical oncology (Northwood, London, England) · 2023Review
- Small Molecule Inhibitors as Therapeutic Agents Targeting Oncogenic Fusion Proteins: Current Status and Clinical.Molecules (Basel, Switzerland) · 2023Review
- The dichotomous role of immunoproteasome in cancer: Friend or foe?Acta pharmaceutica Sinica. B · 2023Review
- The Relevance of Telomerase and Telomere-Associated Proteins in B-Acute Lymphoblastic Leukemia.Genes · 2023Review
- Updates inBiomedicines · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Proteasome inhibitors bortezomib and carfilzomib are approved for the treatment of multiple myeloma and mantle cell lymphoma and have demonstrated clinical efficacy for the treatment of acute lymphoblastic leukemia (ALL). The t(4;11)(q21;q23) chromosomal translocation that leads to the expression of MLL-AF4 fusion protein and confers a poor prognosis, is the major cause of infant ALL. This translocation sensitizes tumor cells to proteasome inhibitors, but toxicities of bortezomib and carfilzomib may limit their use in pediatric patients. Many of these toxicities are caused by on-target inhibition of proteasomes in non-lymphoid tissues (e.g., heart muscle, gut, testicles). We found that MLL-AF4 cells express high levels of lymphoid tissue-specific immunoproteasomes and are sensitive to pharmacologically relevant concentrations of specific immunoproteasome inhibitor ONX-0914, even in the presence of stromal cells. Inhibition of multiple active sites of the immunoproteasomes was required to achieve cytotoxicity against ALL. ONX-0914, an inhibitor of LMP7 (ß5i) and LMP2 (ß1i) sites of the immunoproteasome, and LU-102, inhibitor of proteasome ß2 sites, exhibited synergistic cytotoxicity. Treatment with ONX-0914 significantly delayed the growth of orthotopic ALL xenograft tumors in mice. T-cell ALL lines were also sensitive to pharmacologically relevant concentrations of ONX-0914. This study provides a strong rationale for testing clinical stage immunoproteasome inhibitors KZ-616 and M3258 in ALL.
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Registered trials
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