Evidence map›Paper›PMID 24412926›Full record

ArticleNature medicine2014

Activation of a promyelocytic leukemia-tumor protein 53 axis underlies acute promyelocytic leukemia cure.

Julien Ablain, Kim Rice, Hassane Soilihi, Aurélien de Reynies, Saverio Minucci, Hugues de Thé

Abstract read
PubMed Publisher
In one paragraph

Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed
9.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

101 citing papers in PubMed, 181 citations in OpenAlex.

  1. Arsenic trioxideHaematologica · 2025
    Trial
  2. Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLG-APL2016 Protocol Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021
    Trial
  3. Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Discovery of an LSD1 PROTAC degrader.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. The PML hub: An emerging actor of leukemia therapies.The Journal of experimental medicine · 2023
    Article
  18. Mechanistic update of Trisenox in blood cancer.Current research in pharmacology and drug discovery · 2023
    Review
  19. Article
  20. Review

41 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 2 countries.

Julien Ablain1] Université Paris Diderot, Sorbonne Paris Cité, Hôpital St. Louis, Paris, France. [2] INSERM UMR 944, Equipe Labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St. Louis, Paris, France. [3] CNRS UMR 7212, Hôpital St. Louis, Paris, France. [4].
Kim Rice1] Université Paris Diderot, Sorbonne Paris Cité, Hôpital St. Louis, Paris, France. [2] INSERM UMR 944, Equipe Labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St. Louis, Paris, France. [3] CNRS UMR 7212, Hôpital St. Louis, Paris, France.
Hassane Soilihi1] Université Paris Diderot, Sorbonne Paris Cité, Hôpital St. Louis, Paris, France. [2] INSERM UMR 944, Equipe Labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St. Louis, Paris, France. [3] CNRS UMR 7212, Hôpital St. Louis, Paris, France.
Aurélien de ReyniesProgramme Cartes d'Identité des Tumeurs, Ligue Nationale contre le Cancer, Paris, France.
Saverio Minucci1] Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. [2] Department of Biosciences, University of Milan, Milan, Italy.
Hugues de Thé1] Université Paris Diderot, Sorbonne Paris Cité, Hôpital St. Louis, Paris, France. [2] INSERM UMR 944, Equipe Labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St. Louis, Paris, France. [3] CNRS UMR 7212, Hôpital St. Louis, Paris, France. [4] Assistance Publique Hôpitaux de Paris, Service de Biochimie, Hôpital St. Louis, Paris, France.
Sorbonne Paris Cité · FREuropean Institute of Oncology · ITLa Ligue Contre le Cancer · FRUniversité Paris Cité · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML)-retinoic acid receptor-α (PML-RARA) fusion protein, which interferes with nuclear receptor signaling and PML nuclear body (NB) assembly. APL is the only malignancy definitively cured by targeted therapies: retinoic acid (RA) and/or arsenic trioxide, which both trigger PML-RARA degradation through nonoverlapping pathways. Yet, the cellular and molecular determinants of treatment efficacy remain disputed. We demonstrate that a functional Pml-transformation-related protein 53 (Trp53) axis is required to eradicate leukemia-initiating cells in a mouse model of APL. Upon RA-induced PML-RARA degradation, normal Pml elicits NB reformation and induces a Trp53 response exhibiting features of senescence but not apoptosis, ultimately abrogating APL-initiating activity. Apart from triggering PML-RARA degradation, arsenic trioxide also targets normal PML to enhance NB reformation, which may explain its clinical potency, alone or with RA. This Pml-Trp53 checkpoint initiated by therapy-triggered NB restoration is specific for PML-RARA-driven APL, but not the RA-resistant promyelocytic leukemia zinc finger (PLZF)-RARA variant. Yet, as NB biogenesis is druggable, it could be therapeutically exploited in non-APL malignancies.

Indexed as

AnimalsArsenicalsArsenic TrioxideComputational BiologyHumansKaplan-Meier EstimateLeukemia, Promyelocytic, AcuteMiceMicroarray AnalysisNuclear ProteinsOxidesPromyelocytic Leukemia ProteinProteolysisReceptors, Retinoic AcidRecombinant Fusion ProteinsRetinoic Acid Receptor alphaArsenicalsArsenic TrioxideNuclear ProteinsOxidesPml protein, mousePromyelocytic Leukemia ProteinRARA protein, humanRara protein, mouseReceptors, Retinoic AcidRecombinant Fusion ProteinsRetinoic Acid Receptor alphaTranscription FactorsTretinoinTumor Suppressor Protein p53Tumor Suppressor Proteins

Identifiers

PMID24412926
OpenAlexW2010216204

What OpenQuestion holds

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Registered trials

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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.