ArticleLeukemia2012
Synergistic induction of p53 mediated apoptosis by valproic acid and nutlin-3 in acute myeloid leukemia.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06199557 (A Phase 1/2 Multicenter Open-label Study to Investigate Treatment of Hydroxyurea in Combination With Valproic Acid), which is not on this map. Cited by 53 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
A Phase 1/2 Multicenter Open-label Study to Investigate Treatment of Hydroxyurea in Combination With Valproic Acid (VPA), or 6- Mercaptopurine in Combination With VPA in Patients With AML or HR-MDS Unfit for Standard Therapy
Who cites it
53 citing papers in PubMed, 84 citations in OpenAlex.
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- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
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- A proteolysis-targeting chimera molecule selectively degrades ENL and inhibits malignant gene expression and tumor growth.Journal of hematology & oncology · 2022Article
- Discovery of spirooxindole-derived small-molecule compounds as novel HDAC/MDM2 dual inhibitors and investigation of their anticancer activity.Frontiers in oncology · 2022Article
- Cell Survival and Cell Death at the Intersection of Autophagy and Apoptosis: Implications for Current and Future Cancer Therapeutics.ACS pharmacology & translational science · 2021Review
- Therapeutic Use of Valproic Acid and All-Trans Retinoic Acid in Acute Myeloid Leukemia-Literature Review and Discussion of Possible Use in Relapse after Allogeneic Stem Cell Transplantation.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Article
- Valproic Acid Enhanced Temozolomide-Induced Anticancer Activity in Human Glioma Through the p53-PUMA Apoptosis Pathway.Frontiers in oncology · 2021Article
- Integrated analysis of microRNA and transcription factors in the bone marrow of patients with acute monocytic leukemia.Oncology letters · 2021Article
- P53 in the impaired lungs.DNA repair · 2020Review
- Bifunctional HDAC Therapeutics: One Drug to Rule Them All?Molecules (Basel, Switzerland) · 2020Review
- CD24-targeted fluorescence imaging in patient-derived xenograft models of high-grade serous ovarian carcinoma.EBioMedicine · 2020Article
- Tyrosine kinase inhibitors and interferon-α increase tunneling nanotube (TNT) formation and cell adhesion in chronic myeloid leukemia (CML) cell lines.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Targeting Mouse Double Minute 2: Current Concepts in DNA Damage Repair and Therapeutic Approaches in Cancer.Frontiers in pharmacology · 2020Review
- HDAC Inhibitors in Acute Myeloid Leukemia.Cancers · 2019Review
- Helping the Released Guardian: Drug Combinations for Supporting the Anticancer Activity of HDM2 (MDM2) Antagonists.Cancers · 2019Review
- Modulation of phospho-proteins by interferon-alpha and valproic acid in acute myeloid leukemia.Journal of cancer research and clinical oncology · 2019Article
- Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy.Cancer discovery · 2018Article
- Ex vivo human HSC expansion requires coordination of cellular reprogramming with mitochondrial remodeling and p53 activation.Blood advances · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although TP53 mutations are rare in acute myeloid leukemia (AML), wild type p53 function is habitually annulled through overexpression of MDM2 or through various mechanisms including epigenetic silencing by histone deacetylases (HDACs). We hypothesized that co-inhibition of MDM2 and HDACs, with nutlin-3 and valproic acid (VPA) would additively inhibit growth in leukemic cells expressing wild type TP53 and induce p53-mediated apoptosis. In vitro studies with the combination demonstrated synergistic induction of apoptosis in AML cell lines and patient cells. Nutlin-3 and VPA co-treatment resulted in massive induction of p53, acetylated p53 and p53 target genes in comparison with either agent alone, followed by p53 dependent cell death with autophagic features. In primary AML cells, inhibition of proliferation by the combination therapy correlated with the CD34 expression level of AML blasts. To evaluate the combination in vivo, we developed an orthotopic, NOD/SCID IL2rγ(null) xenograft model of MOLM-13 (AML FAB M5a; wild type TP53) expressing firefly luciferase. Survival analysis and bioluminescent imaging demonstrated the superior in vivo efficacy of the dual inhibition of MDM2 and HDAC in comparison with controls. Our results suggest the concomitant targeting of MDM2-p53 and HDAC inhibition, may be an effective therapeutic strategy for the treatment of AML.
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What OpenQuestion holds
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.