ArticleThe Journal of clinical investigation2025
The NUDIX hydrolase NUDT5 influences purine nucleotide metabolism and thiopurine pharmacology.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- AI-guided discovery of the IRF4-PAICS-LDHA axis as a multitarget hub linking tumor metabolism to CD8+ T cell exhaustion in DLBCL.NPJ precision oncology · 2026Article
- Mitochondrial protein alterations in vascular dementia: evidence from Mendelian randomization, transcriptomics, and a chronic hypoperfusion model.Frontiers in neurologyArticle
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Authors and funding
2 authors.
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Abstract
Purine nucleotides are critical for nucleic acid synthesis, signaling, and cellular metabolism. Thiopurines (TPs), including 6-mercaptopurine and 6-thioguanine, are cornerstone agents for the treatment of acute lymphoblastic leukemia (ALL). TP efficacy and cytotoxicity depend on the metabolism and intracellular activation of TPs, a process influenced by pharmacogenes such as thiopurine-S methyltransferase (TPMT) and NUDIX (nucleoside diphosphates linked to moiety-X) hydrolase 15 (NUDT15). In this issue of the JCI, Maillard et al. identified NUDT5 as a determinant of TP pharmacology. They demonstrated that loss of NUDT5 conferred TP resistance by impairing drug activation and DNA damage responses. Metabolomics studies by Maillard and others revealed that NUDT5 may regulate the balance between the de novo purine synthesis and salvage pathways. Clinically, NUDT5 expression variants were associated with altered TP tolerance. These findings position NUDT5 as a key modulator of nucleotide metabolism and TP efficacy, with potential implications for pharmacogenomics-guided therapy optimization in ALL.
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