ArticleNature medicine2013
Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 papers, 4 of them syntheses that pooled it.
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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
212 citing papers in PubMed, 4 syntheses or guidelines pooled it, 347 citations in OpenAlex.
- Nelarabine in T-cell acute lymphoblastic leukemia: intracellular metabolism and molecular mode-of-action.Leukemia · 2025Pooled it
- Innovating Thiopurine Therapeutic Drug Monitoring: A Systematic Review and Meta-Analysis on DNA-Thioguanine Nucleotides (DNA-TG) as an Inclusive Biomarker in Thiopurine Therapy.Clinical pharmacokinetics · 2024Pooled it
- Pooled it
- NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity.Nature genetics · 2016Pooled it
- Integrated analysis of relapsed B-cell precursor Acute Lymphoblastic Leukemia identifies subtype-specific cytokine and metabolic signatures.Scientific reports · 2019Trial
- Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations.Genome medicine · 2016Trial
- Pediatric T-cell lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation.Haematologica · 2015Trial
- Personalized Therapy with Mercaptopurine in Acute Lymphoblastic Leukemia: Current Advances and Challenges.Current treatment options in oncology · 2026Review
- Article
- Utility of a Digital PCR-Based Gene Expression Panel for Detection of Leukemic Cells in Pediatric Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2026Article
- Review
- The genomic landscape of relapsed infant and childhood KMT2A-rearranged acute leukemia.Nature communications · 2025Article
- Treatment-related mutagenic processes in acute lymphoblastic leukemia.Haematologica · 2025Review
- Nicotinic acid riboside maintains NADCell metabolism · 2025Article
- Genetic evolution and relapse-associated mutations in adult T-cell acute lymphoblastic leukemia patients treated in PETHEMA trials.HemaSphere · 2025Article
- Review
- Subclonal TP53 and KRAS variants combined with poor treatment response identify ultrahigh-risk pediatric patients with T-ALL.Blood advances · 2025Article
- Stattic suppresses p‑STAT3 and induces cell death in T‑cell acute lymphoblastic leukemia.Molecular medicine reports · 2025Article
- Preferential Genetic Pathways Lead to Relapses in Adult B-Cell Acute Lymphoblastic Leukemia.Cancers · 2024Article
- Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL).Experimental & molecular medicine · 2024Review
152 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 10 institutions in 4 countries.
Funding
Abstract
Acute lymphoblastic leukemia (ALL) is an aggressive hematological tumor resulting from the malignant transformation of lymphoid progenitors. Despite intensive chemotherapy, 20% of pediatric patients and over 50% of adult patients with ALL do not achieve a complete remission or relapse after intensified chemotherapy, making disease relapse and resistance to therapy the most substantial challenge in the treatment of this disease. Using whole-exome sequencing, we identify mutations in the cytosolic 5'-nucleotidase II gene (NT5C2), which encodes a 5'-nucleotidase enzyme that is responsible for the inactivation of nucleoside-analog chemotherapy drugs, in 20/103 (19%) relapse T cell ALLs and 1/35 (3%) relapse B-precursor ALLs. NT5C2 mutant proteins show increased nucleotidase activity in vitro and conferred resistance to chemotherapy with 6-mercaptopurine and 6-thioguanine when expressed in ALL lymphoblasts. These results support a prominent role for activating mutations in NT5C2 and increased nucleoside-analog metabolism in disease progression and chemotherapy resistance in ALL.
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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.