ArticleInternational journal of cancer2018
The arginine metabolome in acute lymphoblastic leukemia can be targeted by the pegylated-recombinant arginase I BCT-100.
Article in International journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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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.
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Who cites it
42 citing papers in PubMed, 66 citations in OpenAlex.
- A guide to B cell metabolism.Nature reviews. Immunology · 2026Review
- Nitrogen Isotope Effects in Urea Metabolism: From Biochemistry toInternational journal of molecular sciences · 2026Review
- Metabolic reprogramming of CAR-T cells: a multi-pronged strategy to conquer the immunosuppressive tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Integrative proteomic and metabolomic analysis reveals that ouabain inhibits DLBCL proliferation by reprogramming arginine-driven metabolic networks.Frontiers in pharmacology · 2026Article
- Amino acid metabolic reprogramming drives pathogenesis and therapy in hematologic malignancies.Discover oncology · 2025Review
- Polyamines at the crossroad between cell metabolism and epigenetic regulation in acute leukemias.Cell death discovery · 2025Review
- Biochemistry, pharmacology, and in vivo function of arginases.Pharmacological reviews · 2025Review
- Sestrin3 confers resistance to recombinant human arginase in small cell lung cancer by activating Akt/mTOR/ASS1 axis.PloS one · 2025Article
- Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.International journal of molecular sciences · 2024Review
- Review
- Dysregulated arginine metabolism in precursor B-cell acute lymphoblastic leukemia in children: a metabolomic study.BMC pediatrics · 2024Article
- From the Inside Out: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments.Cold Spring Harbor perspectives in medicine · 2024Review
- Enhancing Leukemia Treatment: The Role of Combined Therapies Based on Amino Acid Starvation.Cancers · 2024Review
- PARC: a phase I/II study evaluating the safety and activity of pegylated recombinant human arginase BCT-100 in relapsed/refractory cancers of children and young adults.Frontiers in oncology · 2024Article
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
- Metabolic crosstalk between stromal and malignant cells in the bone marrow niche.Bone reports · 2023Article
- Review
- Next generation oncolytic viruses expressing PADI1 and TIMP2 exhibit anti-tumor activity against melanoma in nude and humanized mouse models.Molecular therapy oncolytics · 2023Article
- Unveiling tumor immune evasion mechanisms: abnormal expression of transporters on immune cells in the tumor microenvironment.Frontiers in immunology · 2023Review
- Amino acids in hematologic malignancies: Current status and future perspective.Frontiers in nutrition · 2023Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
Arginine is a semi-essential amino acid that plays a key role in cell survival and proliferation in normal and malignant cells. BCT-100, a pegylated (PEG) recombinant human arginase, can deplete arginine and starve malignant cells of the amino acid. Acute lymphoblastic leukemia (ALL) is the most common cancer of childhood, yet for patients with high risk or relapsed disease prognosis remains poor. We show that BCT-100 is cytotoxic to ALL blasts from patients in vitro by necrosis, and is synergistic in combination with dexamethasone. Against ALL xenografts, BCT-100 leads to a reduction in ALL engraftment and a prolongation of survival. ALL blasts express the arginine transporter CAT-1, yet the majority of blasts are arginine auxotrophic due to deficiency in either argininosuccinate synthase (ASS) or ornithine transcarbamylase (OTC). Although endogenous upregulation or retroviral transduced increases in ASS or OTC may promote ALL survival under moderately low arginine conditions, expression of these enzymes cannot prevent BCT-100 cytotoxicity at arginine depleting doses. RNA-sequencing of ALL blasts and supporting stromal cells treated with BCT-100 identifies a number of candidate pathways which are altered in the presence of arginine depletion. Therefore, BCT-100 provides a new clinically relevant therapeutic approach to target arginine metabolism in ALL.
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Registered trials
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.