ArticleHaematologica2021
WEE1 inhibition induces glutamine addiction in T-cell acute lymphoblastic leukemia.
Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Methadone maintenance therapy alters the expression of PLK1 and IFIH1 in patients with heroin addiction: a case-control study.Psychopharmacology · 2026Article
- Glutamine modulates cellular size by regulating Wee1 expression.Scientific reports · 2025Article
- β-Catenin Regulates Glycolytic and Mitochondrial Function in T-Cell Acute Lymphoblastic Leukemia.Biomedicines · 2025Article
- Notch signaling in cancer: metabolic reprogramming and therapeutic implications.Frontiers in immunology · 2025Review
- Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.International journal of molecular sciences · 2024Review
- The glutamate/aspartate transporter EAAT1 is crucial for T-cell acute lymphoblastic leukemia proliferation and survival.Haematologica · 2024Article
- Metabolic regulation of the immune system in health and diseases: mechanisms and interventions.Signal transduction and targeted therapy · 2024Review
- WEE1 Inhibitor Adavosertib Exerts Antitumor Effects on Colorectal Cancer, Especially in Cases withCancers · 2024Article
- XPO1 Enables Adaptive Regulation of mRNA Export Required for Genotoxic Stress Tolerance in Cancer Cells.Cancer research · 2024Article
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Identification of USP29 as a key regulator of nucleotide biosynthesis in neuroblastoma through integrative analysis of multi-omics data.Cancer biology & therapy · 2023Article
- Synergistic interactions of cytarabine-adavosertib in leukemic cell lines proliferation and metabolomic endpoints.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Development of anMolecular therapy. Methods & clinical development · 2023Article
- USP1 promotes the aerobic glycolysis and progression of T-cell acute lymphoblastic leukemia via PLK1/LDHA axis.Blood advances · 2023Article
- Glutamine Metabolism Underlies the Functional Similarity of T Cells between Nile Tilapia and Tetrapod.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- MiR-652-5p elevated glycolysis level by targeting TIGAR in T-cell acute lymphoblastic leukemia.Cell death & disease · 2022Article
- Metabolic reprogramming by miRNAs in the tumor microenvironment: Focused on immunometabolism.Frontiers in oncology · 2022Review
- The LncRNA DUXAP10 Could Function as a Promising Oncogene in Human Cancer.Frontiers in cell and developmental biology · 2022Review
- Insights on Metabolic Reprogramming and Its Therapeutic Potential in Acute Leukemia.International journal of molecular sciences · 2021Review
- MYC in T-cell acute lymphoblastic leukemia: functional implications and targeted strategies.Blood science (Baltimore, Md.) · 2021Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-cell acute lymphoblastic leukemias (T-ALLs) are aggressive and heterogeneous hematologic tumors resulting from the malignant transformation of T-cell progenitors. The major challenges in the treatments of T-ALL are dose-limiting toxicities of chemotherapeutics and drug resistance. Despite important progress in deciphering the genomic landscape of T-ALL, translation of these findings into effective targeted therapies remains largely unsuccessful. New targeted agents with significant antileukemic efficacy and less toxicity are in urgent need. We herein report that the expression of WEE1, a nuclear tyrosine kinase involved in cell cycle G2-M checkpoint signaling, is significantly elevated in T-ALL. Mechanistically, oncogenic MYC directly binds to the WEE1 promoter and activates its transcription. T-ALL cells particularly rely on the elevated WEE1 for cell viability. Pharmacological inhibition of WEE1 elicits global metabolic reprogramming which results in a marked suppression of aerobic glycolysis in T-ALL cells, leading to an increased dependency on glutaminolysis for cell survival. As such, dual targeting of WEE1 and glutaminase (GLS1) induces synergistic lethality in multiple T-ALL cell lines and shows great efficacy in T-ALL patient-derived xenografts. These findings provide mechanistic insights in the regulation of WEE1 kinase in T-ALL and suggest an additional vulnerability during WEE1 inhibitor treatments. In aggregate, we highlight a promising combination strategy of dual inhibition of cell cycle kinase and metabolic enzymes for T-ALL therapeutics.
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