ArticleLeukemia2014
Blocking ETV6/RUNX1-induced MDM2 overexpression by Nutlin-3 reactivates p53 signaling in childhood leukemia.
Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed, 40 citations in OpenAlex.
- FLT4 activation promotes acute lymphoid leukemia survival through stabilization of MDM2/MDMX and inactivation of p53.Oncogenesis · 2025Article
- H1-0 is a specific mediator of the repressive ETV6::RUNX1 transcriptional landscape in preleukemia and B cell acute lymphoblastic leukemia.HemaSphere · 2025Article
- Combination p53 activation and BCL-xLeukemia · 2024Article
- RNA binding protein IGF2BP1 synergizes with ETV6-RUNX1 to drive oncogenic signaling in B-cell Acute Lymphoblastic Leukemia.Journal of experimental & clinical cancer research : CR · 2023Article
- Review
- Review
- Regulome analysis in B-acute lymphoblastic leukemia exposes Core Binding Factor addiction as a therapeutic vulnerability.Nature communications · 2022Article
- Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors.Cancers · 2021Review
- The Expression of P53, MDM2, c-myc, and P14Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2020Article
- MicroRNA Assisted Gene Regulation in Colorectal Cancer.International journal of molecular sciences · 2019Article
- MDM2/X inhibitors under clinical evaluation: perspectives for the management of hematological malignancies and pediatric cancer.Journal of hematology & oncology · 2017Review
- Pathogenesis of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia and mechanisms underlying its relapse.Oncotarget · 2017Review
- Hepatitis B virus X protein promotes the stem-like properties of OV6Cell death & disease · 2017Article
- Pharmacological activation of wild-type p53 in the therapy of leukemia.Experimental hematology · 2016Review
- Identification of lineariifolianoid A as a novel dual NFAT1 and MDM2 inhibitor for human cancer therapy.Journal of biomedical research · 2016Article
- Article
- P53-MDM2 Pathway: Evidences for A New Targeted Therapeutic Approach in B-Acute Lymphoblastic Leukemia.Frontiers in pharmacology · 2016Review
- Bone marrow stroma-derived PGE2 protects BCP-ALL cells from DNA damage-induced p53 accumulation and cell death.Molecular cancer · 2015Article
- Article
- MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway.Cell cycle (Georgetown, Tex.) · 2015Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
ETV6/RUNX1 (E/R) is the most common fusion gene in childhood acute lymphoblastic leukemia. It is responsible for the initiation of leukemia but also indispensable for disease maintenance and propagation, although its function in these latter processes is less clear. We therefore investigated the effects of the perceived p53 pathway alterations in model cell lines and primary leukemias and, in particular, how E/R upregulates MDM2, the predominant negative regulator of p53. We found that E/R transactivates MDM2 in both p53(+/+) and p53(-/-) HCT116 cells by binding to promoter-inherent RUNX1 motifs, which indicates that this activation occurs in a direct and p53-independent manner. Treatment of E/R-positive leukemic cell lines with Nutlin-3, a small molecule that inhibits the MDM2/p53 interaction, arrests their cell cycle and induces apoptosis. These phenomena concur with a p53-induced expression of p21, pro-apoptotic BAX and PUMA, as well as caspase 3 activation and poly ADP-ribose polymerase cleavage. The addition of DNA-damaging and p53-activating chemotherapeutic drugs intensifies apoptosis. Moreover, Nutlin-3 exposure leads to an analogous p53 accumulation and apoptotic surge in E/R-positive primary leukemic cells. Our findings clarify the role of p53 signaling in E/R-positive leukemias and outline the potential basis for its therapeutic exploitation in this setting.
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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.