A dietary pan-amino acid dropout screen in vivo reveals a critical role for histidine in T-ALL

Sep 30, 2026

Uploaded by Pentious

A preprint on bioRxiv describes findings from a dietary pan–amino acid dropout screen performed in vivo to identify nutrients that control T-cell acute lymphoblastic leukemia (T-ALL). The study highlights histidine as a critical dietary component, linking its restriction to strong antileukemic activity. Results indicate that histidine-driven effects are mediated through altered lipid and cholesterol-related metabolic regulation, including downregulation within cholesterol metabolism pathways. The work includes multiple collaborating research groups, author contributions, and funding and licensing information under aCC-BY-NC-ND 4.0.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages54

Reading Time2 h 16 min

AccessFree to download

Study focus

Dietary pan–amino acid dropout screen

Histidine requirement and antileukemic effects

Cholesterol metabolism mediation

bioRxiv preprint doi: [https://doi.org/10.64898/2025.12.21.694897](https://doi.org/10.64898/2025.12.21.694897); this version posted December 23, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 A dietary pan-amino acid dropout screen in vivo reveals a critical role for histidine 2 in T-ALL 3 Authors: Komal Mandleywala 1†, Simona Ulrich2,3†, Victoria da Silva-Diz1†, Puneet 4 Sharma4,5 , Christopher Thai 1,6 , Oekyung Kim 1 , Maya Aleksandrova 1 , Gwendolyn Chung 1 , 5 Cristian Eggers7 , Dieter Lütjohann8 , Tanaya Kulkarni 1 , Amartya Singh 1,6 , M. Elena Díaz- 6 Rubio 1,9 , Michael Wierer10 , Sebastian A. Leidel7 , Xiaoyang Su 1,9 , Eileen P. White 1,11,12 , 7 Joshua D. Rabinowitz 11,13 , Raphael J. Morscher2,3* and Daniel Herranz 1 , 14,15* 8 Affiliations: 9 1 Rutgers Cancer Institute, Rutgers University, New Brunswick, NJ, 08901, USA. 10 2 Pediatric Cancer Metabolism Laboratory, Children's Research Center, University of 11 Zurich, 8008, Zurich, Switzerland. 12 3 Division of Oncology, University Children's Hospital Zurich and Children's Research 13 Center, University of Zurich, 8008, Zurich, Switzerland. 14 4 Department of Biology, Institute of Biochemistry, ETH Zurich, 8093 Zurich, Switzerland 15 5 NCCR RNA and Disease Technology Platform, Bern, Switzerland 16 6Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers 17 University, New Brunswick, NJ, 08901, USA. 18 20892, USA. 19 7 Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of 20 Bern, 3012 Bern, Switzerland 21 8 Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, 22 53127 Bonn, Germany bioRxiv preprint doi: [https://doi.org/10.64898/2025.12.21.694897](https://doi.org/10.64898/2025.12.21.694897); this version posted December 23, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 23 9 Department of Medicine, Rutgers Robert Wood Johnson Medical School, Rutgers 24 University, New Brunswick, NJ, 08901, USA. 25 10 Proteomics Research Infrastructure, Panum Institute, University of Copenhagen, 26 Copenhagen, Denmark 27 11 Ludwig Institute for Cancer Research, Princeton Branch, Princeton University, 28 Princeton, NJ 08544, USA. 29 12 Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 30 08901, USA. 31 13 Department of Chemistry, Princeton University, Princeton, NJ 08544, USA. 32 14 Department of Pharmacology, Rutgers Robert Wood Johnson Medical School, Rutgers 33 University, Piscataway, NJ, 08854, USA. 34 15 Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, Rutgers 35 University, New Brunswick, NJ, 08901, USA. 36 †Equal contribution 37 *Corresponding authors 38 Running title: Dietary histidine restriction exhibits strong antileukemic effects mediated 39 by a downregulation in cholesterol metabolism 40 Keywords: T-cell acute lymphoblastic leukemia, T-ALL, Dietary interventions, Histidine, 41 Cholesterol 42 Financial support: Work in the laboratory of [D.H. is](D.H. is) supported by the US National 43 Institutes of Health (R01CA236936 and R01CA285513), Blood Cancer United, formerly 44 The Leukemia & Lymphoma Society (Scholar Award 1386-23), the V Foundation (T2023- 45 024), the Alex’s Lemonade Stand Foundation (R Award 23-28273) , the Ludwig Cancer bioRxiv preprint doi: [https://doi.org/10.64898/2025.12.21.694897](https://doi.org/10.64898/2025.12.21.694897); this version posted December 23, 2025. The copyright holder for this preprint (which was not certified by peer rev

FAQs

What is the main aim of the study?

To determine which dietary amino-acid changes control T-ALL using an in vivo pan–amino acid dropout screening approach.

Which nutrient is identified as critical?

Histidine is identified as having a critical role in T-ALL under the dietary dropout framework.

How are histidine effects described mechanistically?

The study attributes the antileukemic effects to mediation through downregulation in cholesterol metabolism and related lipid metabolic control.

Sep 30, 2026

Uploaded by Pentious