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| Verfasst von: | Greiner, Georg [VerfasserIn]  |
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| | Witzeneder, Nadine [VerfasserIn] |
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| | Klein, Klara [VerfasserIn] |
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| | Tangermann, Simone [VerfasserIn] |
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| | Kodajova, Petra [VerfasserIn] |
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| | Jaeger, Eva [VerfasserIn] |
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| | Ratzinger, Franz [VerfasserIn] |
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| | Gerner, Marlene C. [VerfasserIn] |
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| | Jawhar, Mohamad [VerfasserIn] |
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| | Baumgartner, Sigrid [VerfasserIn] |
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| | Fruehwirth, Karin [VerfasserIn] |
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| | Schmetterer, Klaus G. [VerfasserIn] |
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| | Zuber, Johannes [VerfasserIn] |
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| | Gleixner, Karoline V. [VerfasserIn] |
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| | Mayerhofer, Matthias [VerfasserIn] |
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| | Schwarzinger, Ilse [VerfasserIn] |
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| | Simonitsch-Klupp, Ingrid [VerfasserIn] |
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| | Esterbauer, Harald [VerfasserIn] |
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| | Baer, Constance [VerfasserIn] |
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| | Walter, Wencke [VerfasserIn] |
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| | Meggendorfer, Manja [VerfasserIn] |
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| | Strassl, Robert [VerfasserIn] |
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| | Haferlach, Torsten [VerfasserIn] |
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| | Hartmann, Karin [VerfasserIn] |
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| | Kenner, Lukas [VerfasserIn] |
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| | Sperr, Wolfgang R. [VerfasserIn] |
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| | Reiter, Andreas [VerfasserIn] |
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| | Sexl, Veronika [VerfasserIn] |
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| | Arock, Michel [VerfasserIn] |
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| | Valent, Peter [VerfasserIn] |
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| | Hoermann, Gregor [VerfasserIn] |
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| Titel: | Tumor necrosis factor α promotes clonal dominance of KIT D816V+ cells in mastocytosis |
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| Titelzusatz: | role of survivin and impact on prognosis |
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| Verf.angabe: | Georg Greiner, Nadine Witzeneder, Klara Klein, Simone Tangermann, Petra Kodajova, Eva Jaeger, Franz Ratzinger, Marlene C. Gerner, Mohamad Jawhar, Sigrid Baumgartner, Karin Fruehwirth, Klaus G. Schmetterer, Johannes Zuber, Karoline V. Gleixner, Matthias Mayerhofer, Ilse Schwarzinger, Ingrid Simonitsch-Klupp, Harald Esterbauer, Constance Baer, Wencke Walter, Manja Meggendorfer, Robert Strassl, Torsten Haferlach, Karin Hartmann, Lukas Kenner, Wolfgang R. Sperr, Andreas Reiter, Veronika Sexl, Michel Arock, Peter Valent, Gregor Hoermann |
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| E-Jahr: | 2024 |
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| Jahr: | March 14 2024 |
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| Umfang: | 12 S. |
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| Fussnoten: | Gesehen am 21.01.2025 |
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| Titel Quelle: | Enthalten in: Blood |
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| Ort Quelle: | Washington, DC : American Society of Hematology, 1946 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 143(2024), 11, Seite 1006-1017 |
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| ISSN Quelle: | 1528-0020 |
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| Abstract: | Systemic mastocytosis (SM) is defined by the expansion and accumulation of neoplastic mast cells (MCs) in the bone marrow (BM) and extracutaneous organs. Most patients harbor a somatic KIT D816V mutation, which leads to growth factor-independent KIT activation and accumulation of MC. Tumor necrosis factor α (TNF) is a proapoptotic and inflammatory cytokine that has been implicated in the clonal selection of neoplastic cells. We found that KIT D816V increases the expression and secretion of TNF. TNF expression in neoplastic MCs is reduced by KIT-targeting drugs. Similarly, knockdown of KIT or targeting the downstream signaling cascade of MAPK and NF-κB signaling reduced TNF expression levels. TNF reduces colony formation in human BM cells, whereas KIT D816V+ cells are less susceptible to the cytokine, potentially contributing to clonal selection. In line, knockout of TNF in neoplastic MC prolonged survival and reduced myelosuppression in a murine xenotransplantation model. Mechanistic studies revealed that the relative resistance of KIT D816V+ cells to TNF is mediated by the apoptosis-regulator BIRC5 (survivin). Expression of BIRC5 in neoplastic MC was confirmed by immunohistochemistry of samples from patients with SM. TNF serum levels are significantly elevated in patients with SM and high TNF levels were identified as a biomarker associated with inferior survival. We here characterized TNF as a KIT D816V-dependent cytokine that promotes clonal dominance. We propose TNF and apoptosis-associated proteins as potential therapeutic targets in SM. |
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| DOI: | doi:10.1182/blood.2023020515 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1182/blood.2023020515 |
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| | Volltext: https://ashpublications.org/blood/article-abstract/143/11/1006/506718/Tumor-necrosis-factor-promotes-clonal-dominance-of ... |
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| | DOI: https://doi.org/10.1182/blood.2023020515 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1915221714 |
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| Verknüpfungen: | → Zeitschrift |
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Tumor necrosis factor α promotes clonal dominance of KIT D816V+ cells in mastocytosis / Greiner, Georg [VerfasserIn]; March 14 2024 (Online-Ressource)
