ArticleLeukemia2023
Inhibition of SUMOylation enhances DNA hypomethylating drug efficacy to reduce outgrowth of hematopoietic malignancies.
Article in Leukemia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Hypomethylating agents in vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS): A systematic review.British journal of haematology · 2026Pooled it
- Review
- SUMOylation inhibitor TAK-981 suppresses proliferation and induces apoptosis in SK-UT-1B uterine leiomyosarcoma cells.Oncology letters · 2026Article
- DAXX promotes SUMOylation of chromatin-trapped DNMT1.Journal of biochemistry · 2026Article
- The impact of epigenetics on tumor metabolism: Friend or foe in drug response?Frontiers in epigenetics and epigenomics · 2026Review
- Integrating gene demethylation and immune modulation: PD-1 nanovesicles as a dual-action therapy for NSCLC.Materials today. Bio · 2025Article
- SUMOylation inhibition potentiates the glucocorticoid receptor to program growth arrest of acute lymphoblastic leukemia cells.Oncogene · 2025Article
- Integrated machine learning and single-cell analysis reveal the prognostic and therapeutic potential of SUMOylation-related genes in ovarian cancer.Frontiers in immunology · 2025Article
- Targeting epigenetic regulation and post-translational modification with 5-Aza-2' deoxycytidine and SUMO E1 inhibition augments T-cell receptor therapy.Journal for immunotherapy of cancer · 2024Article
- Targeted inhibition of SUMOylation: treatment of tumors.Human cell · 2024Review
- Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation.Nature structural & molecular biology · 2024Article
- TOPORS E3 ligase mediates resistance to hypomethylating agent cytotoxicity in acute myeloid leukemia cells.Nature communications · 2024Article
- Inhibition of TOPORS ubiquitin ligase augments the efficacy of DNA hypomethylating agents through DNMT1 stabilization.Nature communications · 2024Article
- SUMO and the DNA damage response.Biochemical Society transactions · 2024Review
- Enzymatic Processing of DNA-Protein Crosslinks.Genes · 2024Review
- SUMOylation inhibitor TAK-981 (subasumstat) synergizes with 5-azacytidine in preclinical models of acute myeloid leukemia.Haematologica · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Combination therapies targeting malignancies aim to increase treatment efficacy and reduce toxicity. Hypomethylating drug 5-Aza-2'-deoxycytidine (5-Aza-2') enhances transcription of tumor suppressor genes and induces replication errors via entrapment of DNMT1, yielding DNA-protein crosslinks. Post-translational modification by SUMO plays major roles in the DNA damage response and is required for degradation of entrapped DNMT1. Here, we combine SUMOylation inhibitor TAK981 and DNA-hypomethylating agent 5-Aza-2'-deoxycytidine to improve treatment of MYC driven hematopoietic malignancies, since MYC overexpressing tumors are sensitive to SUMOylation inhibition. We studied the classical MYC driven malignancy Burkitt lymphoma, as well as diffuse large B-cell lymphoma (DLBCL) with and without MYC translocation. SUMO inhibition prolonged the entrapment of DNMT1 to DNA, resulting in DNA damage. An increase in DNA damage was observed in cells co-treated with TAK981 and 5-Aza-2'. Both drugs synergized to reduce cell proliferation in vitro in a B cell lymphoma cell panel, including Burkitt lymphoma and DLBCL. In vivo experiments combining TAK981 (25 mg/kg) and 5-Aza-2' (2.5 mg/kg) showed a significant reduction in outgrowth of Burkitt lymphoma in an orthotopic xenograft model. Our results demonstrate the potential of tailored combination of drugs, based on insight in molecular mechanisms, to improve the efficacy of cancer therapies.
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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.