ArticleScientific reports2019
Assessment of TP53 lesions for p53 system functionality and drug resistance in multiple myeloma using an isogenic cell line model.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- AcTor, a novel mTOR stimulator, potentiates ixazomib for the treatment of acute myeloid leukemia.Molecular cancer · 2026Article
- AcTor, a novel mTOR stimulator, potentiates ixazomib for the treatment of acute myeloid leukemia.Research square · 2026Article
- Efficacy of melflufen in multiple myeloma with mutated or deleted TP53.Experimental hematology & oncology · 2025Article
- Multi-hit TP53 confers the poorest survival in multiple myeloma in the era of novel therapies.Molecular medicine (Cambridge, Mass.) · 2025Article
- Combined inhibition of CTPS1 and ATR is a metabolic vulnerability in p53-deficient myeloma cells.HemaSphere · 2024Article
- Clonal competition assays identify fitness signatures in cancer progression and resistance in multiple myeloma.HemaSphere · 2024Article
- The Genetic and Molecular Drivers of Multiple Myeloma: Current Insights, Clinical Implications, and the Path Forward.Pharmacogenomics and personalized medicine · 2024Review
- Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis.Blood · 2023Article
- Loss of p53 enhances the tumor-initiating potential and drug resistance of clonogenic multiple myeloma cells.Blood advances · 2023Article
- Article
- Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma.Nature cancer · 2023Article
- Clonal and subclonal TP53 molecular impairment is associated with prognosis and progression in multiple myeloma.Blood cancer journal · 2022Article
- Inhibition of the Protein Arginine Methyltransferase PRMT5 in High-Risk Multiple Myeloma as a Novel Treatment Approach.Frontiers in cell and developmental biology · 2022Article
- Comprehensive CRISPR-Cas9 screens identify genetic determinants of drug responsiveness in multiple myeloma.Blood advances · 2021Article
- Treatment of Multiple Myeloma and the Role of Melphalan in the Era of Modern Therapies-Current Research and Clinical Approaches.Journal of clinical medicine · 2021Review
- p53 expression confers sensitivity to 5-fluorouracil via distinct chromatin accessibility dynamics in human colorectal cancer.Oncology letters · 2021Article
- Long non-coding RNA NEAT1 serves as a novel biomarker for treatment response and survival profiles via microRNA-125a in multiple myeloma.Journal of clinical laboratory analysis · 2020Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent advances in molecular diagnostics have shown that lesions affecting both copies of the gene for tumor suppressor protein 53 (TP53) count among the most powerful predictors for high-risk disease in multiple myeloma (MM). However, the functional relevance and potential therapeutic implications of single hits to TP53 remain less well understood. Here, we have for the first time approximated the different constellations of mono- and bi-allelic TP53 lesions observed in MM patients within the frame of a single MM cell line model and assessed their potential to disrupt p53 system functionality and to impart drug resistance. Both types of common first hit: point mutation with expression of mutant p53 protein or complete loss of contribution from one of two wildtype alleles strongly impaired p53 system functionality and increased resistance to melphalan. Second hits abolished remaining p53 activity and increased resistance to genotoxic drugs even further. These results fit well with the clinical drive to TP53 single- and double-hit disease in MM patients, provide a rationale for the most commonly observed double-hit constellation (del17p+ TP53 point mutation), and underscore the potential increases in MM cell malignancy associated with any type of initial TP53 lesion.
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