ArticleLeukemia2012
AMP-dependent kinase/mammalian target of rapamycin complex 1 signaling in T-cell acute lymphoblastic leukemia: therapeutic implications.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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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.
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
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- The effect of metformin on esophageal cancer risk in patients with type 2 diabetes mellitus: a systematic review and meta‑analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021 · on this mapPooled it
- Molecular Secrets Revealed: How Diabetes may be Paving the Way for Leukemia.Current treatment options in oncology · 2024Review
- Advances in Anti-Cancer Drug Development: Metformin as Anti-Angiogenic Supplemental Treatment for Glioblastoma.International journal of molecular sciences · 2024Review
- Review
- Research Progress on the Use of Metformin in Leukemia Treatment.Current treatment options in oncology · 2024Review
- Article
- Metformin attenuates multiple myeloma cell proliferation and encourages apoptosis by suppressing METTL3-mediated m6A methylation of THRAP3, RBM25, and USP4.Cell cycle (Georgetown, Tex.) · 2023Article
- Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL).International journal of molecular sciences · 2023Review
- Action Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review.Biomolecules · 2023Review
- Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes.Drug design, development and therapy · 2023Review
- Targeting Leukemia-Initiating Cells and Leukemic Niches: The Next Therapy Station for T-Cell Acute Lymphoblastic Leukemia?Cancers · 2022Review
- Metformin and Thymoquinone Synergistically Inhibit Proliferation of Imatinib-Resistant Human Leukemic Cells.Frontiers in pharmacology · 2022Article
- Characterization of a novel glucocorticoid-resistant human B-cell acute lymphoblastic leukemia cell line, with AMPK, mTOR and fatty acid synthesis pathway inhibition.Cancer cell international · 2021Article
- The New Role of AMP-Activated Protein Kinase in Regulating Fat Metabolism and Energy Expenditure in Adipose Tissue.Biomolecules · 2021Review
- Responsiveness to Hedgehog Pathway Inhibitors in T-Cell Acute Lymphoblastic Leukemia Cells Is Highly Dependent on 5'AMP-Activated Kinase Inactivation.International journal of molecular sciences · 2021Article
- Is There A Causal Relationship between Childhood Obesity and Acute Lymphoblastic Leukemia? A Review.Cancers · 2020Review
- Metformin as Potential Therapy for High-Grade Glioma.Cancers · 2020Article
- Metabolic dependencies and vulnerabilities in leukemia.Genes & development · 2019Review
- Mechanisms by Which Obesity Impacts Survival from Acute Lymphoblastic Leukemia.Journal of the National Cancer Institute. Monographs · 2019Review
- A novel method to establish glucocorticoid resistant acute lymphoblastic leukemia cell lines.Journal of experimental & clinical cancer research : CR · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mammalian target of rapamycin (mTOR) serine/threonine kinase is the catalytic subunit of two multi-protein complexes, referred to as mTORC1 and mTORC2. Signaling downstream of mTORC1 has a critical role in leukemic cell biology by controlling mRNA translation of genes involved in both cell survival and proliferation. mTORC1 activity can be downmodulated by upregulating the liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) pathway. Here, we have explored the therapeutic potential of the anti-diabetic drug, metformin (an LKB1/AMPK activator), against both T-cell acute lymphoblastic leukemia (T-ALL) cell lines and primary samples from T-ALL patients displaying mTORC1 activation. Metformin affected T-ALL cell viability by inducing autophagy and apoptosis. However, it was much less toxic against proliferating CD4(+) T-lymphocytes from healthy donors. Western blot analysis demonstrated dephosphorylation of mTORC1 downstream targets. Unlike rapamycin, we found a marked inhibition of mRNA translation in T-ALL cells treated with metformin. Remarkably, metformin targeted the side population of T-ALL cell lines as well as a putative leukemia-initiating cell subpopulation (CD34(+)/CD7(-)/CD4(-)) in patient samples. In conclusion, metformin displayed a remarkable anti-leukemic activity, which emphasizes future development of LKB1/AMPK activators as clinical candidates for therapy in T-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.