ArticleOncotarget2016
P53 activation inhibits all types of hematopoietic progenitors and all stages of megakaryopoiesis.
Article in Oncotarget, 2016. 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, 52 citations in OpenAlex.
- Activating p53Nature communications · 2026Article
- Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.Molecules (Basel, Switzerland) · 2026Review
- Unraveling the role ofHemaSphere · 2026Review
- Targeting the p53 pathway to treat atypical teratoid rhabdoid tumors.Neuro-oncology pediatrics · 2026Article
- Asparaginase and Autophagy Inhibitors Effectively Remove Senescent Cells by Synergistically Limiting Asparagine Supply.Aging cell · 2025Article
- Dual functionality of MDM2 in PROTACs expands the horizons of targeted protein degradation.Biomarker research · 2025Review
- Structure and function of MDM2 and MDM4 in health and disease.The Biochemical journal · 2025Review
- MDM2 inhibition is associated with the emergence of TP53-altered clonal hematopoiesis.NPJ precision oncology · 2025Article
- Discovery and Characterization of Brigimadlin, a Novel and Highly Potent MDM2-p53 Antagonist Suitable for Intermittent Dose Schedules.Molecular cancer therapeutics · 2024Article
- Lessons learned from 20 years of preclinical testing in pediatric cancers.Pharmacology & therapeutics · 2024Review
- A first-in-human phase I study of a novel MDM2/p53 inhibitor alrizomadlin in advanced solid tumors.ESMO open · 2024Article
- Efficacy of Selinexor in Relapsed/Refractory Multiple Myeloma (RRMM) Patients with del17p and Other High-Risk Abnormalities (A Retrospective Single-Center Study).Life (Basel, Switzerland) · 2024Article
- Nanoencapsulation of MDM2 Inhibitor RG7388 and Class-I HDAC Inhibitor Entinostat Enhances their Therapeutic Potential Through Synergistic Antitumor Effects and Reduction of Systemic Toxicity.Molecular pharmaceutics · 2024Article
- Review
- Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution.Nature genetics · 2023Article
- Emerging New Therapeutics for Retinoblastoma.Ocular oncology and pathology · 2022Review
- Review
- Identification of a small-molecule RPL11 mimetic that inhibits tumor growth by targeting MDM2-p53 pathway.Molecular medicine (Cambridge, Mass.) · 2022Article
- Results from a First-in-Human Phase I Study of Siremadlin (HDM201) in Patients with Advanced Wild-Type TP53 Solid Tumors and Acute Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Neurons and glial cells acquire a senescent signature after repeated mild traumatic brain injury in a sex-dependent manner.Frontiers in neuroscience · 2022Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TP53 also known as p53 is a tumor suppressor gene mutated in a variety of cancers. P53 is involved in cell cycle, apoptosis and DNA repair mechanisms and is thus tightly controlled by many regulators. Recently, strategies to treat cancer have focused on the development of MDM2 antagonists to induce p53 stabilization and restore cell death in p53 non-mutated cancers. However, some of these molecules display adverse effects in patients including induction of thrombocytopenia. In the present study, we have explored the effect of SAR405838 not only on human megakaryopoiesis but also more generally on hematopoiesis. We compared its effect to MI-219 and Nutlin, which are less potent MDM2 antagonists than SAR405838. We found that all these compounds induce a deleterious effect on all types of hematopoietic progenitors, as well as on erythroid and megakaryocytic differentiation. Moreover, they inhibit both early and late stages of megakaryopoiesis including ploidization and proplatelet formation. In conclusion, MDM2 antagonists induced a major hematopoietic defect in vitro as well as an inhibition of all stages of megakaryopoiesis that may account for in vivo thrombocytopenia observed in treated patients.
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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.