ArticleBlood advances2022
Single-cell analysis reveals selection of TP53-mutated clones after MDM2 inhibition.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 20 citations in OpenAlex.
- Clonal Metamorphosis: Deconstructing MPN Evolution with Single-Cell and Spatial Multi-Omics.Clinical and experimental medicine · 2026Review
- TP53 isoform dysregulation in pediatric B-ALL: identifying markers of favorable prognosis and relapse-associated dynamic.Molecular biology reports · 2026Article
- Targeting p53 in Cancer: Functional States, Therapeutic Strategies, and Clinical Progress.Cancers · 2026Review
- MDM2 inhibitors in myeloid cancers: from basic biology to clinical use in myeloproliferative neoplasms.Leukemia · 2026Review
- Article
- Unraveling the role ofHemaSphere · 2026Review
- Population PK/PD Modeling for Evaluation of Intertwining Effects of Drug and Disease on Thrombocytopenia in Acute Leukemias.CPT: pharmacometrics & systems pharmacology · 2026Article
- Advances in single-cell DNA sequencing enable insights into human somatic mosaicism.Nature reviews. Genetics · 2025Review
- The TP53 tumor suppressor gene: From molecular biology to clinical investigations.Journal of internal medicine · 2025Review
- CircTADA2A stabilizes p53 via interacting with TRIM28 and suppresses the maintenance of FLT3-ITD acute myeloid leukemia.Leukemia · 2025Article
- MDM2 inhibition is associated with the emergence of TP53-altered clonal hematopoiesis.NPJ precision oncology · 2025Article
- Phase 1 dose escalation study of the MDM2 inhibitor milademetan as monotherapy and in combination with azacitidine in patients with myeloid malignancies.Cancer medicine · 2024Article
- Pharmacological reactivation of p53 in the era of precision anticancer medicine.Nature reviews. Clinical oncology · 2024Review
- Molecular Genetic Profile of Myelofibrosis: Implications in the Diagnosis, Prognosis, and Treatment Advancements.Cancers · 2024Review
- COMPASS: joint copy number and mutation phylogeny reconstruction from amplicon single-cell sequencing data.Nature communications · 2023Article
- Impact of Clonal Architecture on Clinical Course and Prognosis in Patients With Myeloproliferative Neoplasms.HemaSphere · 2023Article
- Review
- Recent advances in therapies for primary myelofibrosis.Faculty reviews · 2023Review
- Hitting the brakes on accelerated and blast-phase myeloproliferative neoplasms: current and emerging concepts.Hematology. American Society of Hematology. Education Program · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms of transformation of chronic myeloproliferative neoplasms (MPN) to leukemia are largely unknown, but TP53 mutations acquisition is considered a key event in this process. p53 is a main tumor suppressor, but mutations in this protein per se do not confer a proliferative advantage to the cells, and a selection process is needed for the expansion of mutant clones. MDM2 inhibitors may rescue normal p53 from degradation and have been evaluated in a variety of cancers with promising results. However, the impact of these drugs on TP53-mutated cells is underexplored. We report herein evidence of a direct effect of MDM2 inhibition on the selection of MPN patients' cells harboring TP53 mutations. To decipher whether these mutations can arise in a specific molecular context, we used a DNA single-cell approach to determine the clonal architecture of TP53-mutated cells. We observed that TP53 mutations are late events in MPN, mainly occurring in the driver clone, whereas clonal evolution frequently consists of sequential branching instead of linear consecutive acquisition of mutations in the same clone. At the single-cell level, the presence of additional mutations does not influence the selection of TP53 mutant cells by MDM2 inhibitor treatment. Also, we describe an in vitro test allowing to predict the emergence of TP53 mutated clones. Altogether, this is the first demonstration that a drug treatment can directly favor the emergence of TP53-mutated subclones in MPN.
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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.