ArticleOncogenesis2017
Synergistic anti-AML effects of the LSD1 inhibitor T-3775440 and the NEDD8-activating enzyme inhibitor pevonedistat via transdifferentiation and DNA rereplication.
Article in Oncogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.
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
9 citing papers in PubMed, 38 citations in OpenAlex.
- Targeting the Glutamine Transporter SLC1A5 Enhances Sensitivity of Acute Myeloid Leukemia to MLN4924.Biomedicines · 2026Article
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- LSD1 inhibitors for cancer treatment: Focus on multi-target agents and compounds in clinical trials.Frontiers in pharmacology · 2023Review
- LncRNA HAS2-AS1 Promotes Glioblastoma Proliferation by Sponging miR-137.Frontiers in oncology · 2021Article
- Cutting Edge Molecular Therapy for Acute Myeloid Leukemia.International journal of molecular sciences · 2020Review
- 4SC-202 induces apoptosis in myelodysplastic syndromes and the underlying mechanism.American journal of translational research · 2020Article
- LSD1/KDM1A inhibitors in clinical trials: advances and prospects.Journal of hematology & oncology · 2019Review
- Eradication of Central Nervous System Leukemia of T-Cell Origin with a Brain-Permeable LSD1 Inhibitor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Epigenetic Modifications in Acute Myeloid Leukemia: Prognosis, Treatment, and Heterogeneity.Frontiers in genetics · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysine-specific demethylase 1A (LSD1, KDM1A) specifically demethylates di- and monomethylated histones H3K4 and K9, resulting in context-dependent transcriptional repression or activation. We previously identified an irreversible LSD1 inhibitor T-3775440, which exerts antileukemic activities in a subset of acute myeloid leukemia (AML) cell lines by inducing cell transdifferentiation. The NEDD8-activating enzyme inhibitor pevonedistat (MLN4924, TAK-924) is an investigational drug with antiproliferative activities in AML, and is also reported to induce cell differentiation. We therefore tested the combination of these two agents in AML models. The combination treatment resulted in synergistic growth inhibition of AML cells, accompanied by enhanced transdifferentiation of an erythroid leukemia lineage into granulomonocytic-like lineage cells. In addition, pevonedistat-induced rereplication stress during the S phase was greatly augmented by concomitant treatment with T-3775440, as reflected by the increased induction of apoptosis. We further demonstrated that the combination treatment was markedly effective in subcutaneous tumor xenograft models as well as in a disseminated model of AML, leading to tumor eradication or prolonged survival in T-3775440/pevonedistat cotreated mice. Our findings indicate the therapeutic potential of the combination of LSD1 inhibitors and pevonedistat for the treatment of AML.
Identifiers
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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.