ArticleCell death & disease2021
Mutant p53-reactivating compound APR-246 synergizes with asparaginase in inducing growth suppression in acute lymphoblastic leukemia cells.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers, 1 of them a synthesis that pooled it.
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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
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Integrating Genomic and Clinical Data in AML: Real-World Application of the Sanger Multistage Model.Genes · 2026Article
- An Integrated Method to Evaluate the Treatment Efficacy and Immunogenicity of B-Cell Acute Lymphoblastic Leukemia Therapeutic Enzyme Formulations.Small methods · 2026Article
- Tumor suppressor network dysregulation in neuroblastoma: molecular mechanisms and precision therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Suppression of ASNS expression by VHL-mediated ubiquitination hinders the progression of renal cell carcinoma through enhancing JUP expression and inhibiting PI3K-AKT and MAPK pathways.International journal of biological sciences · 2026Article
- Covalent Modification of p53 by (ACS pharmacology & translational science · 2024Article
- Gain of Function (GOF) Mutant p53 in Cancer-Current Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Eprenetapopt triggers ferroptosis, inhibits NFS1 cysteine desulfurase, and synergizes with serine and glycine dietary restriction.Science advances · 2022Article
- Review
- Role of p53 in regulation of hematopoiesis in health and disease.Current opinion in hematology · 2022Review
- Targeting Nutrient Dependency in Cancer Treatment.Frontiers in oncology · 2022Review
- Inducing ferroptosis has the potential to overcome therapy resistance in breast cancer.Frontiers in immunology · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
Asparaginase depletes extracellular asparagine in the blood and is an important treatment for acute lymphoblastic leukemia (ALL) due to asparagine auxotrophy of ALL blasts. Unfortunately, resistance occurs and has been linked to expression of the enzyme asparagine synthetase (ASNS), which generates asparagine from intracellular sources. Although TP53 is the most frequently mutated gene in cancer overall, TP53 mutations are rare in ALL. However, TP53 mutation is associated with poor therapy response and occurs at higher frequency in relapsed ALL. The mutant p53-reactivating compound APR-246 (Eprenetapopt/PRIMA-1Met) is currently being tested in phase II and III clinical trials in several hematological malignancies with mutant TP53. Here we present CEllular Thermal Shift Assay (CETSA) data indicating that ASNS is a direct or indirect target of APR-246 via the active product methylene quinuclidinone (MQ). Furthermore, combination treatment with asparaginase and APR-246 resulted in synergistic growth suppression in ALL cell lines. Our results thus suggest a potential novel treatment strategy for 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.