ArticleHaematologica2024
SUMOylation inhibitor TAK-981 (subasumstat) synergizes with 5-azacytidine in preclinical models of acute myeloid leukemia.
Article in Haematologica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 18 citations in OpenAlex.
- Epigenetic Regulation in Acute Myeloid Leukemia: Molecular Mechanisms and Clinical Implications.Cancers · 2026Review
- Transposable elements in hematopoietic stem cells upon aging and myeloid malignancies.Mobile DNA · 2026Review
- SUMOylation Inhibitor TAK-981 Alleviates Hallmark Features of Preeclampsia Related to High Glucocorticoid Exposure by Inhibiting Placental Oxidative Stress in Rats.Antioxidants (Basel, Switzerland) · 2026Article
- Deciphering the Ubiquitin-like Code of DNA-PK: Mechanisms and Therapeutic Opportunities.Biomolecules · 2026Review
- SAE1 emerges as a pan-cancer driver and key regulator of HCC metastasis.Journal of advanced research · 2026Article
- Post-translational modification networks in tumor radiosensitivity: mechanistic insights and therapeutic opportunities.Journal of translational medicine · 2026Review
- Targeting SUMOylation Triggers IFN-β-dependent Activation of Patient and Allogenic NK Cells in Preclinical Models of Acute Myeloid Leukemia.Molecular cancer therapeutics · 2026Article
- Post-translational modifications at the crossroads of cancer metabolism and immune regulation: therapeutic opportunities and challenges.International journal of surgery (London, England) · 2026Review
- One-carbon metabolism in cancer: moonlighting functions of metabolic enzymes and anti-tumor therapy.Cancer metastasis reviews · 2025Review
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- Synthetic inhibition of the SUMO pathway by targeting the SAE1 component via TAK-981 compound impairs growth and chemosensitizes embryonal and alveolar rhabdomyosarcoma cell lines.Molecular and cellular biochemistry · 2025Article
- Immune regulation by the SUMO family.Nature reviews. Immunology · 2025Review
- SUMOylation Regulates Neutrophil Phagocytosis and Migration.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Quantitation of TAK-981 in human plasma via LC-MS/MS and its application in clinical trials.Bioanalysis · 2025Article
- SUMOylation facilitates the stability of BCR-ABL to promote chronic myeloid leukemia progression.Oncogene · 2025Article
- The impact of dysregulation SUMOylation on prostate cancer.Journal of translational medicine · 2025Review
- Diagnostic and Therapeutic Implications of the SUMOylation Pathway in Acute Myeloid Leukemia.Cancers · 2025Review
- Tendomodulin in pan-cancer analysis: exploring its impact on immune modulation and uncovering functional insights in colorectal cancer.BMC cancer · 2025Article
- The SUMO Family: Mechanisms and Implications in Thyroid Cancer Pathogenesis and Therapy.Biomedicines · 2024Review
- Inhibition of TOPORS ubiquitin ligase augments the efficacy of DNA hypomethylating agents through DNMT1 stabilization.Nature communications · 2024Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemias (AML) are severe hematomalignancies with dismal prognosis. The post-translational modification SUMOylation plays key roles in leukemogenesis and AML response to therapies. Here, we show that TAK-981 (subasumstat), a first-in-class SUMOylation inhibitor, is endowed with potent anti-leukemic activity in various preclinical models of AML. TAK-981 targets AML cell lines and patient blast cells in vitro and in vivo in xenografted mice with minimal toxicity on normal hematopoietic cells. Moreover, it synergizes with 5-azacytidine (AZA), a DNA-hypomethylating agent now used in combination with the BCL-2 inhibitor venetoclax to treat AML patients unfit for standard chemotherapies. Interestingly, TAK-981+AZA combination shows higher anti-leukemic activity than AZA+venetoclax combination both in vitro and in vivo, at least in the models tested. Mechanistically, TAK-981 potentiates the transcriptional reprogramming induced by AZA, promoting apoptosis, alteration of the cell cycle and differentiation of the leukemic cells. In addition, TAK-981+AZA treatment induces many genes linked to inflammation and immune response pathways. In particular, this leads to the secretion of type-I interferon by AML cells. Finally, TAK-981+AZA induces the expression of natural killer-activating ligands (MICA/B) and adhesion proteins (ICAM-1) at the surface of AML cells. Consistently, TAK-981+AZA-treated AML cells activate natural killer cells and increase their cytotoxic activity. Targeting SUMOylation with TAK-981 may thus be a promising strategy to both sensitize AML cells to AZA and reduce their immune-escape capacities.
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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.