Evidence map›Paper›PMID 41509383›Full record

ArticlebioRxiv : the preprint server for biology2025

A dietary pan-amino acid dropout screen

Komal Mandleywala, Simona Ulrich, Victoria da Silva-Diz, Puneet Sharma, Christopher Thai, Oekyung Kim, Maya Aleksandrova, Gwendolyn Chung, Cristian Eggers, Dieter Lütjohann and 10 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

20 authors.

Komal MandleywalaRutgers Cancer Institute, Rutgers University, New Brunswick, NJ, 08901, USA.
Simona UlrichPediatric Cancer Metabolism Laboratory, Children's Research Center, University of Zurich, 8008, Zurich, Switzerland.
Victoria da Silva-DizRutgers Cancer Institute, Rutgers University, New Brunswick, NJ, 08901, USA.
Puneet SharmaDepartment of Biology, Institute of Biochemistry, ETH Zurich, 8093 Zurich, Switzerland.
Christopher ThaiRutgers Cancer Institute, Rutgers University, New Brunswick, NJ, 08901, USA.
Oekyung KimRutgers Cancer Institute, Rutgers University, New Brunswick, NJ, 08901, USA.
Maya AleksandrovaRutgers Cancer Institute, Rutgers University, New Brunswick, NJ, 08901, USA.
Gwendolyn ChungRutgers Cancer Institute, Rutgers University, New Brunswick, NJ, 08901, USA.
Cristian EggersDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, 3012 Bern, Switzerland.
Dieter LütjohannInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, 53127 Bonn, Germany.
Tanaya KulkarniRutgers Cancer Institute, Rutgers University, New Brunswick, NJ, 08901, USA.
Amartya SinghRutgers Cancer Institute, Rutgers University, New Brunswick, NJ, 08901, USA.
M Elena Díaz-RubioRutgers Cancer Institute, Rutgers University, New Brunswick, NJ, 08901, USA.
Michael WiererProteomics Research Infrastructure, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Sebastian A LeidelDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, 3012 Bern, Switzerland.ORCID 0000-0002-0523-6325
Xiaoyang SuRutgers Cancer Institute, Rutgers University, New Brunswick, NJ, 08901, USA.
Eileen P WhiteRutgers Cancer Institute, Rutgers University, New Brunswick, NJ, 08901, USA.
Joshua D RabinowitzLudwig Institute for Cancer Research, Princeton Branch, Princeton University, Princeton, NJ 08544, USA.
Raphael J MorscherPediatric Cancer Metabolism Laboratory, Children's Research Center, University of Zurich, 8008, Zurich, Switzerland.
Daniel HerranzRutgers Cancer Institute, Rutgers University, New Brunswick, NJ, 08901, USA.ORCID 0000-0003-1768-5969

Funding

TRANSCRIPTIONAL PROFILINGP30CA072720 · NCI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI Chang S Chan · 1997 to 2026
$94.5M
The role of glutaminolysis as a therapeutic target in T-ALLR01CA236936 · NCI · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI HERRANZ, DANIEL · 2019 to 2023
$1.8M
The role of pyruvate kinase as a therapeutic target in T-ALLR01CA285513 · NCI · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI Daniel Herranz · 2024 to 2026
$1.1M
NCI NIH HHS P30 CA072720NCI NIH HHS R01 CA236936NCI NIH HHS R01 CA285513
6 · The paper itself

Abstract

Dietary interventions show therapeutic potential in cancer, but systematic comparisons are lacking. We performed a dietary pan-amino acid dropout screen in an orthotopic model of NOTCH1-driven T-cell acute lymphoblastic leukemia and identified histidine depletion as uniquely antileukemic. Histidine-restricted diets extended survival of leukemic mice in a dose-dependent manner, while remaining well-tolerated. Mechanistically, multiomic profiling revealed that histidine deprivation-induced ribosome stalling activates GCN2 to suppress cholesterol biosynthesis pathways critical for leukemic proliferation. Dietary cholesterol supplementation partially reverted the antileukemic effects of histidine restriction

Indexed as

CholesterolDietary interventionsHistidineT-ALLT-cell acute lymphoblastic leukemia

Identifiers

PMID41509383
PMCPMC12776171

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.