ArticleNature cancer2021
Chemotherapy and mismatch repair deficiency cooperate to fuel TP53 mutagenesis and ALL relapse.
Article in Nature cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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.
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Who cites it
36 citing papers in PubMed, 47 citations in OpenAlex.
- Comparative efficacy and long-term survival of CD19/22 versus CD19 CAR-T immunotherapy in Relapsed/Refractory B-ALL with TP53 alterations.Journal of translational medicine · 2026Trial
- Impact of p53 Target Genes on Drug Resistance in TP53-Mutated B-Cell Precursor Acute Lymphoblastic Leukemia.Cancer medicine · 2026Article
- Genomic profiling of Mexican patients with B-cell precursor acute lymphoblastic leukemia reveals clinically significant somatic and potential germline variants.The journal of pathology. Clinical research · 2026Article
- Therapy-Related Mutational Signatures in Subsequent Neoplasms among Survivors of Childhood Cancer.Cancer discovery · 2026Article
- Combined inhibition of de novo pyrimidine synthesis and ATR promotes ATF4-mediated cell death inHemaSphere · 2026Article
- ZNF184 negatively regulates HR repair and predicts poor prognosis in acute lymphoblastic leukemia.Nucleic acids research · 2026Article
- Measurement of mitochondria amount and clearance using flow cytometry: effect of mitophagy inhibitors in leukemia cells.Cancer & metabolism · 2026Article
- Interplay between monocyte subsets and leukemic blasts shapes the immune microenvironment and sustains minimal residual disease in pediatric B-cell acute lymphoblastic leukemia.Frontiers in immunology · 2026Article
- Complex genotype-phenotype relationships shape the response to treatment of down syndrome childhood acute lymphoblastic leukaemia.Scientific reports · 2025Article
- A single non-coding SNP in FPGS modulates folate drug efficacy in acute lymphoblastic leukemia: data-driven exploration and experimental validation.Molecular biomedicine · 2025Article
- 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
- Decoding Molecular Interactions: Unraveling the Crosstalk between the Wnt Pathway and Key Signaling Networks by miRNA in Colorectal Cancer Progression.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Unraveling mutagenic processes influencing the tumor mutational patterns of individuals with constitutional mismatch repair deficiency.Nature communications · 2025Article
- Review
- Conventional chemotherapy: millions of cures, unresolved therapeutic index.Nature reviews. Cancer · 2025Review
- Multi-omics analyses reveal biological and clinical insights in recurrent stage I non-small cell lung cancer.Nature communications · 2025Article
- Article
- Pharmacogenomics in Pediatric Oncology Research and Treatment.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2024Article
- Twenty years of Gendicine® rAd-p53 cancer gene therapy: The first-in-class human cancer gene therapy in the era of personalized oncology.Genes & diseases · 2024Review
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Authors and funding
27 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemotherapy is a standard treatment for pediatric acute lymphoblastic leukemia (ALL), which sometimes relapses with chemoresistant features. However, whether acquired drug-resistance mutations in relapsed ALL pre-exist or are induced by treatment remains unknown. Here we provide direct evidence of a specific mechanism by which chemotherapy induces drug-resistance-associated mutations leading to relapse. Using genomic and functional analysis of relapsed ALL we show that thiopurine treatment in mismatch repair (MMR)-deficient leukemias induces hotspot TP53 R248Q mutations through a specific mutational signature (thio-dMMR). Clonal evolution analysis reveals sequential MMR inactivation followed by TP53 mutation in some patients with ALL. Acquired TP53 R248Q mutations are associated with on-treatment relapse, poor treatment response and resistance to multiple chemotherapeutic agents, which could be reversed by pharmacological p53 reactivation. Our findings indicate that TP53 R248Q in relapsed ALL originates through synergistic mutagenesis from thiopurine treatment and MMR deficiency and suggest strategies to prevent or treat TP53-mutant relapse.
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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.