ArticleCancer cell2018
Structure and Mechanisms of NT5C2 Mutations Driving Thiopurine Resistance in Relapsed Lymphoblastic Leukemia.
Article in Cancer cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
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
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- Association ofHaematologica · 2024Pooled it
- Pooled it
- Personalized Therapy with Mercaptopurine in Acute Lymphoblastic Leukemia: Current Advances and Challenges.Current treatment options in oncology · 2026Review
- ASS1-derived argininosuccinate promotes purine nucleoside synthesis in B cell acute lymphoblastic leukaemia.Nature metabolism · 2026Article
- Review
- Exploring the shared genetic architecture between testosterone traits and major depressive disorder.BMC psychiatry · 2025Article
- Synthesis of N-Doped Graphene Quantum Dots from Cellulose and Construction of a Fluorescent Probe for 6-Mercaptopurin Quantitative Detection.Materials (Basel, Switzerland) · 2024Article
- An Alternatively Spliced Gain-of-Function NT5C2 Isoform Contributes to Chemoresistance in Acute Lymphoblastic Leukemia.Cancer research · 2024Article
- Histidine re-sensitizes pediatric acute lymphoblastic leukemia to 6-mercaptopurine through tetrahydrofolate consumption and SIRT5-mediated desuccinylation.Cell death & disease · 2024Article
- Modulation of nucleotide metabolism by picornaviruses.PLoS pathogens · 2024Article
- N, S, Br co-doped carbon dots: One-step synthesis and fluorescent detection of 6-mercaptopurine in tablet.Journal of pharmaceutical analysis · 2024Article
- Comprehensive genomic characterization of hematologic malignancies at a pediatric tertiary care center.Frontiers in oncology · 2024Article
- Pharmacologic Inhibition of NT5C2 Reverses Genetic and Nongenetic Drivers of 6-MP Resistance in Acute Lymphoblastic Leukemia.Cancer discovery · 2022Article
- Spectrum of Genetic Mutations in Korean Pediatric Acute Lymphoblastic Leukemia.Journal of clinical medicine · 2022Article
- Article
- Resistance Mechanisms in Pediatric B-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2022Review
- NUDT15 polymorphism and NT5C2 and PRPS1 mutations influence thiopurine sensitivity in acute lymphoblastic leukaemia cells.Journal of cellular and molecular medicine · 2021Article
- Oncogenic Mechanisms and Therapeutic Targeting of Metabolism in Leukemia and Lymphoma.Cold Spring Harbor perspectives in medicine · 2021Review
- Effects of NT5C2 Germline Variants on 6-Mecaptopurine Metabolism in Children With Acute Lymphoblastic Leukemia.Clinical pharmacology and therapeutics · 2021Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Activating mutations in the cytosolic 5'-nucleotidase II gene NT5C2 drive resistance to 6-mercaptopurine in acute lymphoblastic leukemia. Here we demonstrate that constitutively active NT5C2 mutations K359Q and L375F reconfigure the catalytic center for substrate access and catalysis in the absence of allosteric activator. In contrast, most relapse-associated mutations, which involve the arm segment and residues along the surface of the inter-monomeric cavity, disrupt a built-in switch-off mechanism responsible for turning off NT5C2. In addition, we show that the C-terminal acidic tail lost in the Q523X mutation functions to restrain NT5C2 activation. These results uncover dynamic mechanisms of enzyme regulation targeted by chemotherapy resistance-driving NT5C2 mutations, with important implications for the development of NT5C2 inhibitor therapies.
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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.