ArticleCancer research2021
NPM-ALK-Induced Reprogramming of Mature TCR-Stimulated T Cells Results in Dedifferentiation and Malignant Transformation.
Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 18 citations in OpenAlex.
- CircRNAs derived from the tyrosine phosphatase PTPN22 impact chemosensitivity in ALK-positive T-cell lymphomas.Scientific reports · 2026Article
- Identification of biomarkers related to amino acid metabolism in nonobstructive azoospermia by bioinformatics.Medicine · 2026Article
- Nucleophosmin 1 proteins as potential therapeutic targets in non-communicable chronic inflammatory diseases: a review of pathophysiological mechanisms.Frontiers in cell and developmental biology · 2026Review
- ALK in cancer: from function to therapeutic targeting.Nature reviews. Cancer · 2025Review
- UBASH3B-mediated MRPL12 Y60 dephosphorylation inhibits LUAD development by driving mitochondrial metabolism reprogramming.Journal of experimental & clinical cancer research : CR · 2024Article
- The gene expression profile and cell of origin of canine peripheral T-cell lymphoma.BMC cancer · 2024Article
- Identification and validation of SHC1 and FGFR1 as novel immune-related oxidative stress biomarkers of non-obstructive azoospermia.Frontiers in endocrinology · 2024Article
- Diverse and reprogrammable mechanisms of malignant cell transformation in lymphocytes: pathogenetic insights and translational implications.Frontiers in oncology · 2024Review
- Chimeric antigen receptors enable superior control of HIV replication by rapidly killing infected cells.PLoS pathogens · 2023Article
- Chimeric kinase ALK induces expression of NAMPT and selectively depends on this metabolic enzyme to sustain its own oncogenic function.Leukemia · 2023Article
- Aberrant expression of GOLM1 protects ALK+ anaplastic large cell lymphoma from apoptosis by enhancing BCL-XL stability.Blood advances · 2023Article
- Combined disruption of T cell inflammatory regulators Regnase-1 and Roquin-1 enhances antitumor activity of engineered human T cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Updates in pathobiological aspects of anaplastic large cell lymphoma.Frontiers in oncology · 2023Review
- PSMA-targeting TGFβ-insensitive armored CAR T cells in metastatic castration-resistant prostate cancer: a phase 1 trial.Nature medicine · 2022Article
- De novo generation of the NPM-ALK fusion recapitulates the pleiotropic phenotypes of ALK+ ALCL pathogenesis and reveals the ROR2 receptor as target for tumor cells.Molecular cancer · 2022Article
- Regulation of CD45 phosphatase by oncogenic ALK in anaplastic large cell lymphoma.Frontiers in oncology · 2022Article
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16 authors at 2 institutions in 1 country.
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Abstract
Fusion genes including NPM-ALK can promote T-cell transformation, but the signals required to drive a healthy T cell to become malignant remain undefined. In this study, we introduce NPM-ALK into primary human T cells and demonstrate induction of the epithelial-to-mesenchymal transition (EMT) program, attenuation of most T-cell effector programs, reemergence of an immature epigenomic profile, and dynamic regulation of c-Myc, E2F, and PI3K/mTOR signaling pathways early during transformation. A mutant of NPM-ALK failed to bind several signaling complexes including GRB2/SOS, SHC1, SHC4, and UBASH3B and was unable to transform T cells. Finally, T-cell receptor (TCR)-generated signals were required to achieve T-cell transformation, explaining how healthy individuals can harbor T cells with NPM-ALK translocations. These findings describe the fundamental mechanisms of NPM-ALK-mediated oncogenesis and may serve as a model to better understand factors that regulate tumor formation. SIGNIFICANCE: This investigation into malignant transformation of T cells uncovers a requirement for TCR triggering, elucidates integral signaling complexes nucleated by NPM-ALK, and delineates dynamic transcriptional changes as a T cell transforms.
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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.