ArticleScience advances2015
Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia.
Article in Science advances, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Zidovudine and Interferon Alfa based regimens for the treatment of adult T-cell leukemia/lymphoma (ATLL): a systematic review and meta-analysis.Virology journal · 2023Pooled it
- Replication Stress Tolerance in Adult T-Cell Leukemia.Biomolecules · 2026Review
- Targeting Genome Maintenance Defects of Cancers Using Chain-Terminating Nucleoside Analogs.Cancer science · 2026Review
- Unmasking HAM/TSP: understanding HTLV-1-driven neurological disease.Journal of neurovirology · 2026Review
- Abacavir enhances the efficacy of doxorubicin via inhibition of histone demethylase KDM5B in breast cancer.Scientific reports · 2025Article
- Upregulation of YY1/EZH2 and MLH1 as Therapeutic Targets for Adult T-Cell Leukemia/Lymphoma.Cancer science · 2025Article
- TDP1 splice-site mutation causes HAP1 cell hypersensitivity to topoisomerase I inhibition.Nucleic acids research · 2025Article
- RAD18- and BRCA1-dependent pathways promote cellular tolerance to the nucleoside analog ganciclovir.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- REV3 promotes cellular tolerance to 5-fluorodeoxyuridine by activating translesion DNA synthesis and intra-S checkpoint.PLoS genetics · 2024Article
- A comparative study of different antiviral treatment protocols in HCV related cryoglobulinemic vasculitis.Scientific reports · 2024Article
- HTLV-1 bZIP factor impairs DNA mismatch repair system.Biochemical and biophysical research communications · 2023Article
- Activation of PERK-ATF4-CHOP pathway as a novel therapeutic approach for efficient elimination of HTLV-1-infected cells.Blood advances · 2020Article
- Mammalian Tyrosyl-DNA Phosphodiesterases in the Context of Mitochondrial DNA Repair.International journal of molecular sciences · 2019Review
- CtIP-BRCA1 complex and MRE11 maintain replication forks in the presence of chain terminating nucleoside analogs.Nucleic acids research · 2019Article
- Tyrosyl-DNA phosphodiesterases: rescuing the genome from the risks of relaxation.Nucleic acids research · 2018Review
- Dual inhibition of the mTORC1 and mTORC2 signaling pathways is a promising therapeutic target for adult T-cell leukemia.Cancer science · 2018Article
- TDP1 is Critical for the Repair of DNA Breaks Induced by Sapacitabine, a Nucleoside also Targeting ATM- and BRCA-Deficient Tumors.Molecular cancer therapeutics · 2017Article
- HTLV-1 bZIP factor suppresses TDP1 expression through inhibition of NRF-1 in adult T-cell leukemia.Scientific reports · 2017Article
- The dominant role of proofreading exonuclease activity of replicative polymerase ε in cellular tolerance to cytarabine (Ara-C).Oncotarget · 2017Article
- Repriming by PrimPol is critical for DNA replication restart downstream of lesions and chain-terminating nucleosides.Cell cycle (Georgetown, Tex.) · 2016Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adult T cell leukemia (ATL) is an aggressive T cell malignancy caused by human T cell leukemia virus type 1 (HTLV-1) and has a poor prognosis. We analyzed the cytotoxic effects of various nucleoside analog reverse transcriptase inhibitors (NRTIs) for HIV-1 on ATL cells and found that abacavir potently and selectively kills ATL cells. Although NRTIs have minimal genotoxicities on host cells, the therapeutic concentration of abacavir induced numerous DNA double-strand breaks (DSBs) in the chromosomal DNA of ATL cells. DSBs persisted over time in ATL cells but not in other cell lines, suggesting impaired DNA repair. We found that the reduced expression of tyrosyl-DNA phosphodiesterase 1 (TDP1), a repair enzyme, is attributable to the cytotoxic effect of abacavir on ATL cells. We also showed that TDP1 removes abacavir from DNA ends in vitro. These results suggest a model in which ATL cells with reduced TDP1 expression are unable to excise abacavir incorporated into genomic DNA, leading to irreparable DSBs. On the basis of the above mechanism, we propose abacavir as a promising chemotherapeutic agent for ATL.
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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.