Evidence map›Paper›PMID 38057495›Full record

ArticleLeukemia2024

ACOX1-mediated peroxisomal fatty acid oxidation contributes to metabolic reprogramming and survival in chronic lymphocytic leukemia.

Mariana Tannoury, Marianne Ayoub, Léa Dehgane, Ivan Nemazanyy, Kenza Dubois, Charlotte Izabelle, Aurélie Brousse, Damien Roos-Weil, Karim Maloum, Hélène Merle-Béral and 6 more

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In one paragraph

Article in Leukemia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
6.6field-weighted citation impact, top 3% 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

15 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
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  10. Peroxisome Dysfunction and Steatotic Liver Disease.International journal of molecular sciences · 2025
    Review
  11. Article
  12. Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025
    Review
  13. Article
  14. Article
  15. Article
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

16 authors at 3 institutions in 1 country.

Mariana TannouryCentre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, F-75006, Paris, France.
Marianne Ayoub *Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, F-75006, Paris, France.
Léa Dehgane *Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, F-75006, Paris, France.
Ivan NemazanyyStructure Fédérative de Recherche Necker, INSERM US24/CNRS UAR 3633, Platform for Metabolic Analyses, F-75015, Paris, France.ORCID http://orcid.org/0000-0001-8080-839X
Kenza DuboisCentre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, F-75006, Paris, France.ORCID http://orcid.org/0009-0000-8288-5217
Charlotte IzabelleFaculté de Pharmacie, Université Paris Cité, PICMO, US 25 Inserm, UAR 3612 CNRS, F-75006, Paris, France.
Aurélie BrousseCentre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, F-75006, Paris, France.
Damien Roos-WeilCentre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, F-75006, Paris, France.
Karim MaloumCentre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, F-75006, Paris, France.ORCID http://orcid.org/0000-0001-8864-4801
Hélène Merle-BéralCentre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, F-75006, Paris, France.
Brigitte BauvoisCentre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, F-75006, Paris, France.
Bruno SaubameaFaculté de Pharmacie, Université Paris Cité, PICMO, US 25 Inserm, UAR 3612 CNRS, F-75006, Paris, France.
Elise ChapiroCentre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, F-75006, Paris, France.ORCID http://orcid.org/0000-0003-3427-7596
Florence Nguyen-KhacCentre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, F-75006, Paris, France.ORCID http://orcid.org/0000-0003-3107-6668
Delphine GarnierCentre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, F-75006, Paris, France.ORCID http://orcid.org/0000-0002-5744-5612
Santos A SusinCentre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, F-75006, Paris, France. santos.susin@inserm.fr.ORCID http://orcid.org/0000-0002-3366-1628
Inserm · FRDélégation Paris 5 · FRCentre National de la Recherche Scientifique · FR

Funding

Association Laurette Fugain (Laurette Fugain) ALF 2020/08Ligue Contre le Cancer RS19/75-59
6 · The paper itself

Abstract

Chronic lymphocytic leukemia (CLL) is still an incurable disease, with many patients developing resistance to conventional and targeted therapies. To better understand the physiology of CLL and facilitate the development of innovative treatment options, we examined specific metabolic features in the tumor CLL B-lymphocytes. We observed metabolic reprogramming, characterized by a high level of mitochondrial oxidative phosphorylation activity, a low glycolytic rate, and the presence of C2- to C6-carnitine end-products revealing an unexpected, essential role for peroxisomal fatty acid beta-oxidation (pFAO). Accordingly, downmodulation of ACOX1 (a rate-limiting pFAO enzyme overexpressed in CLL cells) was enough to shift the CLL cells' metabolism from lipids to a carbon- and amino-acid-based phenotype. Complete blockade of ACOX1 resulted in lipid droplet accumulation and caspase-dependent death in CLL cells, including those from individuals with poor cytogenetic and clinical prognostic factors. In a therapeutic translational approach, ACOX1 inhibition spared non-tumor blood cells from CLL patients but led to the death of circulating, BCR-stimulated CLL B-lymphocytes and CLL B-cells receiving pro-survival stromal signals. Furthermore, a combination of ACOX1 and BTK inhibitors had a synergistic killing effect. Overall, our results highlight a less-studied but essential metabolic pathway in CLL and pave the way towards the development of new, metabolism-based treatment options.

Indexed as

Leukemia, Lymphocytic, Chronic, B-CellAcyl-CoA OxidaseB-LymphocytesFatty AcidsHumansMetabolic ReprogrammingMitochondriaACOX1 protein, humanAcyl-CoA OxidaseFatty Acids

Identifiers

PMID38057495
OpenAlexW4389399001

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.