ArticleHaematologica2022
APR-246 induces early cell death by ferroptosis in acute myeloid leukemia.
Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
126 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Mutant TP53 hijacks RNA-splicing factor RBM28 to suppress double-stranded RNA triggered antitumor immunity.Nature communications · 2026Article
- The KDM-family inhibitor JIB-04 sensitizes AML cells to venetoclax by inducing a ferroptosis-like phenotype.Blood neoplasia · 2026Article
- A Tale of Two Mechanisms: The p53 Modulator COTI-2 Is a Zn Metallochaperone.Drug development research · 2026Article
- Eprenetapopt in combination with Palbociclib exerts synthetic lethality in mantle cell lymphoma.Translational oncology · 2026Article
- Stearoyl-CoA desaturase 1 integrates tissue-specific oncogenic pathways into a pan-cancer ferroptosis resistance program.Cell death & disease · 2026Review
- Targeting p53 in Cancer: Functional States, Therapeutic Strategies, and Clinical Progress.Cancers · 2026Review
- Unveiling Candidate Markers for Drug Resistance or Synthetic Lethality in Cervical Cancer: Integrative Analysis of Genetic and Pharmacoprofiling.Cancer reports (Hoboken, N.J.) · 2026Article
- Wild-Type p53 Protein Enhances APR-246-Induced Cytotoxicity in Acute Myeloid Leukemia and Normal Hematopoietic Stem/Progenitor Cells.International journal of molecular sciences · 2026Article
- Unbiased assessment of APR-246 responsive p53 mutants in ovarian cancer.Cell death discovery · 2026Article
- Potential diagnostic, prognostic, and therapeutic implications of ferroptosis in myelodysplastic syndromes.Discover oncology · 2026Review
- Genetic mutations governing ferroptosis sensitivity and resistance: a precision approach to cancer therapy.Cell death & disease · 2026Review
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Dual targeting of GPX4 and TXNRD1 triggers eradication of AML cells through induction of apoptosis and ferroptosis.Experimental hematology & oncology · 2026Article
- Looking at the fraction with Annexin V⁺ and propidium iodide⁺: insights into cell death types from preclinical studies in solid and haematological cancers.Apoptosis : an international journal on programmed cell death · 2026Review
- Single-cell profiling reveals reprogrammed hierarchy and disrupted immune-stromal ecosystem in TP53-mutated AML.Experimental hematology & oncology · 2026Article
- Mutant p53 Regulates Pyruvate Dehydrogenase Kinase 1 (PDK1) to Promote Proliferation and Migration in Breast Cancer.Cancer science · 2026Article
- UBC9 silencing-mediated PPARα deSUMOylation induces inhibition of cell proliferation by ferroptosis in acute myeloid leukemia.Archives of medical science : AMS · 2026Article
- Harnessing ferroptosis for cancer therapy: Mechanisms and therapeutic strategies (Review).Oncology reports · 2026Review
66 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
APR-246 is a promising new therapeutic agent that targets p53 mutated proteins in myelodysplastic syndromes and in acute myeloid leukemia (AML). APR-246 reactivates the transcriptional activity of p53 mutants by facilitating their binding to DNA target sites. Recent studies in solid cancers have found that APR-246 can also induce p53-independent cell death. In this study, we demonstrate that AML cell death occurring early after APR-246 exposure is suppressed by iron chelators, lipophilic antioxidants and inhibitors of lipid peroxidation, and correlates with the accumulation of markers of lipid peroxidation, thus fulfilling the definition of ferroptosis, a recently described cell death process. The capacity of AML cells to detoxify lipid peroxides by increasing their cystine uptake to maintain major antioxidant molecule glutathione biosynthesis after exposure to APR-246 may be a key determinant of sensitivity to this compound. The association of APR-246 with induction of ferroptosis (either by pharmacological compounds, or genetic inactivation of SLC7A11 or GPX4) had a synergistic effect on the promotion of cell death, both in vivo and ex vivo.
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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.