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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.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/a-dietary-pan-amino-acid-dropout-screen-in-vivo-reveals-a-critical-role-for-histidine-in-t-all/451344/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/a-dietary-pan-amino-acid-dropout-screen-in-vivo-reveals-a-critical-role-for-histidine-in-t-all/451344.png","ImageObject",300,407,{"name":92,"@type":93},"Pentious","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main aim of the study?","Question",{"text":112,"@type":113},"To determine which dietary amino-acid changes control T-ALL using an in vivo pan–amino acid dropout screening approach.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which nutrient is identified as critical?",{"text":117,"@type":113},"Histidine is identified as having a critical role in T-ALL under the dietary dropout framework.",{"name":119,"@type":110,"acceptedAnswer":120},"How are histidine effects described mechanistically?",{"text":121,"@type":113},"The study attributes the antileukemic effects to mediation through downregulation in cholesterol metabolism and related lipid metabolic control.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},451344,1791076341,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1374404730887,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","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  \navailable under aCC-BY-NC-ND 4.0 International license.  \n1 A dietary pan-amino acid dropout screen in vivo reveals a critical role for histidine  \n2 in T-ALL  \n3 Authors: Komal Mandleywala 1†, Simona Ulrich2,3†, Victoria da Silva-Diz1†, Puneet  \n4 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*  \n8 Affiliations:  \n9 1 Rutgers Cancer Institute, Rutgers University, New Brunswick, NJ, 08901, USA.  \n10 2 Pediatric Cancer Metabolism Laboratory, Children's Research Center, University of  \n11 Zurich, 8008, Zurich, Switzerland.  \n12 3 Division of Oncology, University Children's Hospital Zurich and Children's Research  \n13 Center, University of Zurich, 8008, Zurich, Switzerland.  \n14 4 Department of Biology, Institute of Biochemistry, ETH Zurich, 8093 Zurich, Switzerland  \n15 5 NCCR RNA and Disease Technology Platform, Bern, Switzerland  \n16 6Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers  \n17 University, New Brunswick, NJ, 08901, USA.  \n18 20892, USA.  \n19 7 Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of  \n20 Bern, 3012 Bern, Switzerland  \n21 8 Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, 22 53127 Bonn, Germany  \nbioRxiv 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  \navailable under aCC-BY-NC-ND 4.0 International license.  \n23 9 Department of Medicine, Rutgers Robert Wood Johnson Medical School, Rutgers  \n24 University, New Brunswick, NJ, 08901, USA.  \n25 10 Proteomics Research Infrastructure, Panum Institute, University of Copenhagen, 26 Copenhagen, Denmark  \n27 11 Ludwig Institute for Cancer Research, Princeton Branch, Princeton University, 28 Princeton, NJ 08544, USA.  \n29 12 Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ  \n30 08901, USA.  \n31 13 Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.  \n32 14 Department of Pharmacology, Rutgers Robert Wood Johnson Medical School, Rutgers  \n33 University, Piscataway, NJ, 08854, USA.  \n34 15 Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, Rutgers  \n35 University, New Brunswick, NJ, 08901, USA.  \n36 †Equal contribution  \n37 *Corresponding authors  \n38 Running title: Dietary histidine restriction exhibits strong antileukemic effects mediated  \n39 by a downregulation in cholesterol metabolism  \n40 Keywords: T-cell acute lymphoblastic leukemia, T-ALL, Dietary interventions, Histidine,  \n41 Cholesterol  \n42 Financial support: Work in the laboratory of [D.H. is](D.H. is) supported by the US National  \n43 Institutes of Health (R01CA236936 and R01CA285513), Blood Cancer United, formerly  \n44 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  \nbioRxiv 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","cbCaiuEgWp2rMJPk","https://ap.wps.com/l/cbCaiuEgWp2rMJPk","pdf",3340964,54,"English","# Study focus\n## Dietary pan–amino acid dropout screen\n## Histidine requirement and antileukemic effects\n## Cholesterol metabolism mediation","[{\"question\":\"What is the main aim of the study?\",\"answer\":\"To determine which dietary amino-acid changes control T-ALL using an in vivo pan–amino acid dropout screening approach.\"},{\"question\":\"Which nutrient is identified as critical?\",\"answer\":\"Histidine is identified as having a critical role in T-ALL under the dietary dropout framework.\"},{\"question\":\"How are histidine effects described mechanistically?\",\"answer\":\"The study attributes the antileukemic effects to mediation through downregulation in cholesterol metabolism and related lipid metabolic control.\"}]","A dietary pan-amino acid dropout screen in vivo reveals a critical role for histidine in T-ALL | PDF",1790734928,136]