ArticleProceedings of the National Academy of Sciences of the United States of America2010
Requirement for deoxycytidine kinase in T and B lymphocyte development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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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
60 citing papers in PubMed, 91 citations in OpenAlex.
- A pilot clinical trial of oral tetrahydrouridine/decitabine for noncytotoxic epigenetic therapy of chemoresistant lymphoid malignancies.Seminars in hematology · 2021Trial
- Physiological folate levels constrain nucleotide synthesis and increase dependence on nucleotide salvage.bioRxiv : the preprint server for biology · 2026Article
- A complex mutational signature generated by cytarabine resistance.NAR cancer · 2026Article
- Deoxycytidine kinase inhibition: Rewiring tumor nucleotide metabolism for therapeutic gain.Nucleosides, nucleotides & nucleic acids · 2026Review
- Review
- Landscape of targets within nucleoside metabolism for the modification of immune responses.Frontiers in oncology · 2025Review
- The DNA Methyltransferase Inhibitor 5-Aza-4'-thio-2'-Deoxycytidine Induces C>G Transversions and Acute Lymphoid Leukemia Development.Cancer research · 2024Article
- Inactivation of cytidine triphosphate synthase 1 prevents fatal auto-immunity in mice.Nature communications · 2024Article
- ATR kinase supports normal proliferation in the early S phase by preventing replication resource exhaustion.Nature communications · 2023Article
- Targeting deoxycytidine kinase improves symptoms in mouse models of multiple sclerosis.Immunology · 2023Article
- Different Susceptibility of T and B Cells to Cladribine Depends On Their Levels of Deoxycytidine Kinase Activity Linked to Activation Status.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022Article
- Article
- Imaging of T-cell Responses in the Context of Cancer Immunotherapy.Cancer immunology research · 2021Review
- Non-invasive biomarkers for monitoring the immunotherapeutic response to cancer.Journal of translational medicine · 2020Review
- The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review.Drugs · 2020Review
- The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review.Drugs · 2020Review
- Chemical Embryology Redux: Metabolic Control of Development.Trends in genetics : TIG · 2020Review
- DCK is a promising prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma.World journal of surgical oncology · 2020Article
- Article
- Approaches to PET Imaging of Glioblastoma.Molecules (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Deoxycytidine kinase (dCK) is a rate-limiting enzyme in deoxyribonucleoside salvage, a metabolic pathway that recycles products of DNA degradation. dCK phosphorylates and therefore activates nucleoside analog prodrugs frequently used in cancer, autoimmunity, and viral infections. In contrast to its well established therapeutic relevance, the biological function of dCK remains enigmatic. Highest levels of dCK expression are found in thymus and bone marrow, indicating a possible role in lymphopoiesis. To test this hypothesis we generated and analyzed dCK knockout (KO) mice. dCK inactivation selectively and profoundly affected T and B cell development. A 90-fold decrease in thymic cellularity was observed in the dCK KO mice relative to wild-type littermates. Lymphocyte numbers in the dCK KO mice were 5- to 13-fold below normal values. The severe impact of dCK inactivation on lymphopoiesis was unexpected given that nucleoside salvage has been thought to play a limited, "fine-tuning" role in regulating deoxyribonucleotide triphosphate pools produced by the de novo pathway. The dCK KO phenotype challenges this view and indicates that, in contrast to the great majority of other somatic cells, normal lymphocyte development critically requires the deoxyribonucleoside salvage pathway.
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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.