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| Verfasst von: | Bruch, Peter-Martin [VerfasserIn]  |
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| | Giles, Holly AR [VerfasserIn] |
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| | Kolb, Carolin [VerfasserIn] |
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| | Herbst, Sophie [VerfasserIn] |
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| | Becirovic, Tina [VerfasserIn] |
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| | Roider, Tobias [VerfasserIn] |
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| | Lu, Junyan [VerfasserIn] |
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| | Scheinost, Sebastian [VerfasserIn] |
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| | Wagner, Lena [VerfasserIn] |
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| | Huellein, Jennifer [VerfasserIn] |
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| | Berest, Ivan [VerfasserIn] |
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| | Kriegsmann, Mark [VerfasserIn] |
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| | Kriegsmann, Katharina [VerfasserIn] |
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| | Zgorzelski, Christiane [VerfasserIn] |
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| | Dreger, Peter [VerfasserIn] |
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| | Zaugg, Judith B. [VerfasserIn] |
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| | Müller-Tidow, Carsten [VerfasserIn] |
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| | Zenz, Thorsten [VerfasserIn] |
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| | Huber, Wolfgang [VerfasserIn] |
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| | Dietrich, Sascha [VerfasserIn] |
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| Titel: | Drug-microenvironment perturbations reveal resistance mechanisms and prognostic subgroups in CLL |
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| Verf.angabe: | Peter-Martin Bruch, Holly AR Giles, Carolin Kolb, Sophie A Herbst, Tina Becirovic, Tobias Roider, Junyan Lu, Sebastian Scheinost, Lena Wagner, Jennifer Huellein, Ivan Berest, Mark Kriegsmann, Katharina Kriegsmann, Christiane Zgorzelski, Peter Dreger, Judith B Zaugg, Carsten Müller-Tidow, Thorsten Zenz, Wolfgang Huber & Sascha Dietrich |
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| E-Jahr: | 2022 |
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| Jahr: | 12 August 2022 |
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| Umfang: | 20 S. |
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| Fussnoten: | Gesehen am 20.03.2023 |
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| Titel Quelle: | Enthalten in: Molecular systems biology |
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| Ort Quelle: | [London] : Nature Publishing Group UK, 2005 |
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| Jahr Quelle: | 2022 |
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| Band/Heft Quelle: | 18(2022), 8 vom: 1. Aug., Artikel-ID e10855, Seite 1-20 |
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| ISSN Quelle: | 1744-4292 |
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| Abstract: | Abstract The tumour microenvironment and genetic alterations collectively influence drug efficacy in cancer, but current evidence is limited and systematic analyses are lacking. Using chronic lymphocytic leukaemia (CLL) as a model disease, we investigated the influence of 17 microenvironmental stimuli on 12 drugs in 192 genetically characterised patient samples. Based on microenvironmental response, we identified four subgroups with distinct clinical outcomes beyond known prognostic markers. Response to multiple microenvironmental stimuli was amplified in trisomy 12 samples. Trisomy 12 was associated with a distinct epigenetic signature. Bromodomain inhibition reversed this epigenetic profile and could be used to target microenvironmental signalling in trisomy 12 CLL. We quantified the impact of microenvironmental stimuli on drug response and their dependence on genetic alterations, identifying interleukin 4 (IL4) and Toll-like receptor (TLR) stimulation as the strongest actuators of drug resistance. IL4 and TLR signalling activity was increased in CLL-infiltrated lymph nodes compared with healthy samples. High IL4 activity correlated with faster disease progression. The publicly available dataset can facilitate the investigation of cell-extrinsic mechanisms of drug resistance and disease progression. |
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| DOI: | doi:10.15252/msb.202110855 |
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| URL: | kostenfrei: Volltext: https://doi.org/10.15252/msb.202110855 |
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| | kostenfrei: Volltext: https://www.embopress.org/doi/full/10.15252/msb.202110855 |
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| | DOI: https://doi.org/10.15252/msb.202110855 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | chronic lymphocytic leukaemia |
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| | drug perturbation |
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| | microenvironment |
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| | multi-omics |
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| | trisomy 12 |
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| K10plus-PPN: | 1839540540 |
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| Verknüpfungen: | → Zeitschrift |
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| Lokale URL UB: |  Zum Volltext |
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Drug-microenvironment perturbations reveal resistance mechanisms and prognostic subgroups in CLL / Bruch, Peter-Martin [VerfasserIn]; 12 August 2022 (Online-Ressource)
