ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2022
Different Susceptibility of T and B Cells to Cladribine Depends On Their Levels of Deoxycytidine Kinase Activity Linked to Activation Status.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Treg Susceptibility to Cladribine-Induced Depletion Correlates With Therapy Response in Patients With Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Unique expression pattern of circulating exosomal miRNA correlates with CNS pathology.Frontiers in immunology · 2026Article
- Cladribine Tablets Mode of Action, Learning from the Pandemic: A Narrative Review.Neurology and therapy · 2023Review
- Single-cell profiling reveals preferential reduction of memory B cell subsets in cladribine patients that correlates with treatment response.Therapeutic advances in neurological disorders · 2023Article
- The NT5DC family: expression profile and prognostic value in pancreatic adenocarcinoma.Journal of Cancer · 2023Article
- Mass cytometry reveals cladribine-induced resets among innate lymphoid cells in multiple sclerosis.Scientific reports · 2022Article
- Cladribine treatment improves cortical network functionality in a mouse model of autoimmune encephalomyelitis.Journal of neuroinflammation · 2022Article
- Solute Carrier Nucleoside Transporters in Hematopoiesis and Hematological Drug Toxicities: A Perspective.Cancers · 2022Review
- Cladribine Tablets for Relapsing-Remitting Multiple Sclerosis: A Clinician's Review.Neurology and therapy · 2022Review
- Cladribine as a Potential Object of Nucleoside Transporter-Based Drug Interactions.Clinical pharmacokinetics · 2022Review
- Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deoxycytidine kinase (dCK) and 5' deoxynucleotidase (NT5C2) are involved in metabolism of cladribine (2CdA), the immunomodulatory drug for multiple sclerosis; by mediating phosphorylation (activation) or phosphorolysis (deactivation) of 2CdA, respectively, these enzymes promote or prevent its accumulation in the cell, which leads to cell death. In particular, lymphocytes which present with a high intracellular dCK/NT5C2 ratio are more sensitive to 2CdA than other immune cells. We aim at determining if the expression of these enzymes and/or their activity differ in specific progenitor and mature immune cells and are influenced by cellular activation and/or exposure to 2CdA. Flow cytometry analysis showed no difference in dCK/NT5C2 ratio in progenitor and mature immune cells. 2CdA induced apoptosis in stimulated T and B cells and unstimulated B cells. dCK expression was enhanced by 2CdA at mRNA and protein levels in activated T cells and mRNA level in activated B cells. dCK activity, measured through an in-house luminescence release enzyme assay was higher in activated T and B cells, and such an increase was abrogated in activated B cells, but not T cells, upon exposure to 2CdA. These results reveal an important relationship between dCK activity and the effect of 2CdA on B and T cells, according to their activation status. Further study is warranted to evaluate whether dCK activity could, in the future, be a suitable predictive biomarker of lymphocyte response to 2CdA.
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