Evidence map›Paper›PMID 40185100›Full record

ArticleCell2025

PAX translocations remodel mitochondrial metabolism through altered leucine usage in rhabdomyosarcoma.

Bhargab Kalita, Gerard Martinez-Cebrian, Justina McEvoy, Melody Allensworth, Michelle Knight, Alessandro Magli, Rita C R Perlingeiro, Michael A Dyer, Elizabeth Stewart, Brian David Dynlacht

Abstract read
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–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

11 citing papers in PubMed.

  1. ANKRD11 deficiency reprograms CD8Nature immunology · 2026
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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

10 authors.

Bhargab KalitaDepartment of Pathology and Perlmutter Cancer Institute, New York University School of Medicine, New York, NY 10016, USA. Electronic address: bhargab.kalita@nyulangone.org.
Gerard Martinez-CebrianDepartment of Pathology and Perlmutter Cancer Institute, New York University School of Medicine, New York, NY 10016, USA; Josep Carreras Leukaemia Research Institute, 08916 Badalona, Spain.
Justina McEvoyDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 323, Memphis, TN 38105, USA.
Melody AllensworthDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 323, Memphis, TN 38105, USA.
Michelle KnightDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 323, Memphis, TN 38105, USA; Department of Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Alessandro MagliDepartment of Medicine, Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA; Genomic Medicine Unit, Sanofi, 225nd Avenue, Waltham, MA 02451, USA.
Rita C R PerlingeiroDepartment of Medicine, Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
Michael A DyerDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 323, Memphis, TN 38105, USA.
Elizabeth StewartDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 323, Memphis, TN 38105, USA; Department of Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: elizabeth.stewart@stjude.org.
Brian David DynlachtDepartment of Pathology and Perlmutter Cancer Institute, New York University School of Medicine, New York, NY 10016, USA. Electronic address: brian.dynlacht@nyulangone.org.

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
In Vivo Testing of Novel Drug Combinations for Pediatric Soft Tissue SarcomasU01CA263969 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Michael A Dyer, Elizabeth A Stewart · 2021 to 2026
$4.0M
Novel Therapeutic Approaches for the Treatment of NeuroblastomaR01CA248432 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI DYER, MICHAEL A · 2020 to 2024
$2.4M
Exploring networks underlying muscle stem cell identity - Resubmission - 1R01AR076954 · NIAMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DYNLACHT, BRIAN D · 2021 to 2025
$2.3M
Novel Therapeutic Approaches for the Treatment of RhabdomyosarcomaR01CA219686 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI DYER, MICHAEL A · 2017 to 2021
$2.0M
Modeling Retinoblastoma Initiation Using 3D-Retinal OrganoidsR01CA245508 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI DYER, MICHAEL A · 2020 to 2024
$2.0M
NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA219686NCI NIH HHS R01 CA245508NCI NIH HHS R01 CA248432NCI NIH HHS U01 CA263969NIAMS NIH HHS R01 AR076954
6 · The paper itself

Abstract

Alveolar rhabdomyosarcoma (ARMS) patients harboring paired-box fusion proteins (PAX3/7-FOXO1) exhibit a greater incidence of tumor relapse, metastasis, and poor survival outcome, thereby underscoring the urgent need to develop effective therapies to treat this subtype of childhood cancer. To uncover mechanisms that contribute to tumor initiation, we develop a muscle progenitor model and use epigenomic approaches to unravel genome rewiring events mediated by PAX3/7 fusion proteins. Among the key targets of PAX3/7 fusion proteins, we identify a cohort of oncogenes, fibroblast growth factor (FGF) receptors, tRNA-modifying enzymes, and genes essential for mitochondrial metabolism and protein translation, which we successfully targeted in preclinical trials. We identify leucine usage as a key factor driving the growth of aggressive PAX-fusion tumors, as limiting its bioavailability impaired oxidative phosphorylation and mitochondrial metabolism, delaying tumor progression and improving survival in vivo. Our data provide a compelling list of actionable targets and suggest promising new strategies to treat this tumor.

Indexed as

LeucineMitochondriaOncogene Proteins, FusionPAX3 Transcription FactorRhabdomyosarcomaRhabdomyosarcoma, AlveolarAnimalsCell Line, TumorFemaleHumansMiceOxidative PhosphorylationPAX7 Transcription FactorTranslocation, GeneticLeucineOncogene Proteins, FusionPAX3 protein, humanPAX3 Transcription FactorPAX7 Transcription Factor3D/2D-adapted PDX modelsalveolar rhabdomyosarcomaLeucinemitochondrial metabolismMYCNmyogenic progenitorsroblitinibtigecyclineTRMT5tRNA modifications

Identifiers

PMID40185100
PMCPMC12085299

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.