ArticleLeukemia2012
Valproic acid induces differentiation and transient tumor regression, but spares leukemia-initiating activity in mouse models of APL.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
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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
29 citing papers in PubMed, 56 citations in OpenAlex.
- Reawakening Differentiation Therapy in Acute Myeloid Leukemia: A Comprehensive Review of ATRA-Based Combination Strategies.Current oncology (Toronto, Ont.) · 2026Review
- OXPHOS mediators in acute myeloid leukemia patients: Prognostic biomarkers and therapeutic targets for personalized medicine.World journal of surgical oncology · 2024Article
- Synergy of retinoic acid and BH3 mimetics in MYC(N)-driven embryonal nervous system tumours.British journal of cancer · 2024Article
- Caloric restriction leads to druggable LSD1-dependent cancer stem cells expansion.Nature communications · 2024Article
- Function of PML-RARA in Acute Promyelocytic Leukemia.Advances in experimental medicine and biology · 2024Review
- Co-targeting leukemia-initiating cells and leukemia bulk leads to disease eradication.Leukemia · 2022Article
- Roles of Histone Deacetylases in Acute Myeloid Leukemia With Fusion Proteins.Frontiers in oncology · 2021Review
- Evolving Chemotherapy Free Regimens for Acute Promyelocytic Leukemia.Frontiers in oncology · 2021Review
- Article
- Epigenetics in myelodysplastic syndromes.Seminars in cancer biology · 2018Review
- Differentiation therapy revisited.Nature reviews. Cancer · 2018Review
- Analysis of the interplay between all-trans retinoic acid and histone deacetylase inhibitors in leukemic cells.Archives of toxicology · 2017Article
- Histone Acetyltransferase p300/CREB-binding Protein-associated Factor (PCAF) Is Required for All-The Journal of biological chemistry · 2017Article
- Selective Inhibitors of Histone Deacetylases 1 and 2 Synergize with Azacitidine in Acute Myeloid Leukemia.PloS one · 2017Article
- Anticancer effects of valproic acid on oral squamous cell carcinoma via SUMOylationExperimental and therapeutic medicine · 2016Article
- Inhibition of histone deacetylases in cancer therapy: lessons from leukaemia.British journal of cancer · 2016Review
- Epigenetics in acute promyelocytic leukaemia pathogenesis and treatment response: a TRAnsition to targeted therapies.British journal of cancer · 2015Review
- Antagonism between granulocytic maturation and deacetylase inhibitor-induced apoptosis in acute promyelocytic leukaemia cells.British journal of cancer · 2015Article
- Unlocking the potential of retinoic acid in anticancer therapy.British journal of cancer · 2014Review
- Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders.Nature reviews. Drug discovery · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant histone acetylation was physiopathologically associated with the development of acute myeloid leukemias (AMLs). Reversal of histone deacetylation by histone deacetylase inhibitor (HDACis) activates a cell death program that allows tumor regression in mouse models of AMLs. We have used several models of PML-RARA-driven acute promyelocytic leukemias (APLs) to analyze the in vivo effects of valproic acid, a well-characterized HDACis. Valproic acid (VPA)-induced rapid tumor regression and sharply prolonged survival. However, discontinuation of treatment was associated to an immediate relapse. In vivo, as well as ex vivo, VPA-induced terminal granulocytic differentiation. Yet, despite full differentiation, leukemia-initiating cell (LIC) activity was actually enhanced by VPA treatment. In contrast to all-trans retinoic acid (ATRA) or arsenic, VPA did not degrade PML-RARA. However, in combination with ATRA, VPA synergized for PML-RARA degradation and LIC eradication in vivo. Our studies indicate that VPA triggers differentiation, but spares LIC activity, further uncouple differentiation from APL clearance and stress the importance of PML-RARA degradation in APL cure.
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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.