Evidence map›Paper›PMID 33053669›Full record

ArticleCancers2020

Dendrogenin A Enhances Anti-Leukemic Effect of Anthracycline in Acute Myeloid Leukemia.

Pierre-Luc Mouchel, Nizar Serhan, Rémy Betous, Thomas Farge, Estelle Saland, Philippe De Medina, Jean-Sébastien Hoffmann, Jean-Emmanuel Sarry, Marc Poirot, Sandrine Silvente-Poirot and 1 more

Abstract read
In one paragraph

Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Exploring the nexus of nuclear receptors in hematological malignancies.Cellular and molecular life sciences : CMLS · 2024
    Review
  5. Review
  6. The dual role of autophagy in acute myeloid leukemia.Journal of hematology & oncology · 2022
    Review
  7. Article
  8. Review
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Pierre-Luc MouchelService d'Hématologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, 31059 Toulouse, France.ORCID 0000-0001-7832-9146
Nizar SerhanCentre de Recherches en Cancérologie de Toulouse, UMR1037, Inserm, Université de Toulouse 3 Paul Sabatier, Equipe Labellisée LIGUE 2018, F-31037 Toulouse, France.
Rémy BetousCRCT, Université de Toulouse, Inserm, CNRS, UPS, 31000 Toulouse, France.
Thomas FargeCentre de Recherches en Cancérologie de Toulouse, UMR1037, Inserm, Université de Toulouse 3 Paul Sabatier, Equipe Labellisée LIGUE 2018, F-31037 Toulouse, France.
Estelle SalandCentre de Recherches en Cancérologie de Toulouse, UMR1037, Inserm, Université de Toulouse 3 Paul Sabatier, Equipe Labellisée LIGUE 2018, F-31037 Toulouse, France.
Philippe De MedinaAffichem SAS, 31400 Toulouse, France.
Jean-Sébastien HoffmannLaboratoire d'Excellence Toulouse Cancer (TOUCAN), Laboratoire de pathologie, Institut Universitaire du Cancer-Toulouse, Oncopole, 31037 Toulouse, France.ORCID 0000-0003-2222-354X
Jean-Emmanuel SarryCentre de Recherches en Cancérologie de Toulouse, UMR1037, Inserm, Université de Toulouse 3 Paul Sabatier, Equipe Labellisée LIGUE 2018, F-31037 Toulouse, France.
Marc PoirotTeam "Cholesterol Metabolism and Therapeutic Innovations", Cancer Research Center of Toulouse (CRCT), UMR 1037, Inserm-Université de Toulouse 3, Equipe labellisée par la ligue contre le cancer, 31037 Toulouse, France.ORCID 0000-0002-5711-6624
Sandrine Silvente-PoirotTeam "Cholesterol Metabolism and Therapeutic Innovations", Cancer Research Center of Toulouse (CRCT), UMR 1037, Inserm-Université de Toulouse 3, Equipe labellisée par la ligue contre le cancer, 31037 Toulouse, France.
Christian RécherService d'Hématologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, 31059 Toulouse, France.ORCID 0000-0002-3332-4525

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dendrogenin A (DDA), a mammalian cholesterol metabolite with tumor suppressor properties, has recently been shown to exhibit strong anti-leukemic activity in acute myeloid leukemia (AML) cells by triggering lethal autophagy. Here, we demonstrated that DDA synergistically enhanced the toxicity of anthracyclines in AML cells but not in normal hematopoietic cells. Combination index of DDA treatment with either daunorubicin or idarubicin indicated a strong synergism in KG1a, KG1 and MV4-11 cell lines. This was confirmed in vivo using immunodeficient mice engrafted with MOLM-14 cells as well as in a panel of 20 genetically diverse AML patient samples. This effect was dependent on Liver X Receptor β, a major target of DDA. Furthermore, DDA plus idarubicin strongly increased p53BP1 expression and the number of DNA strand breaks in alkaline comet assays as compared to idarubicin alone, whereas DDA alone was non-genotoxic. Mechanistically, DDA induced JNK phosphorylation and the inhibition of AKT phosphorylation, thereby maximizing DNA damage induced by idarubicin and decreasing DNA repair. This activated autophagic cell death machinery in AML cells. Overall, this study shows that the combination of DDA and idarubicin is highly promising and supports clinical trials of dendrogenin A in AML patients.

Indexed as

AMLanthracyclineautophagyCLDXDDAdendrogenin ADNA damageLXRprimary samplesynergy

Identifiers

PMID33053669
PMCPMC7601603

What OpenQuestion holds

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Registered trials

None linked

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.