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| Verfasst von: | Streuer, Alexander [VerfasserIn]  |
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| | Jann, Johann-Christoph [VerfasserIn] |
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| | Boch, Tobias [VerfasserIn] |
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| | Mossner, Maximilian [VerfasserIn] |
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| | Riabov, Vladimir [VerfasserIn] |
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| | Schmitt, Nanni [VerfasserIn] |
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| | Altrock, Eva [VerfasserIn] |
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| | Xu, Qingyu [VerfasserIn] |
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| | Demmerle, Marie [VerfasserIn] |
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| | Nowak, Verena [VerfasserIn] |
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| | Obländer, Julia [VerfasserIn] |
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| | Palme, Iris [VerfasserIn] |
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| | Weimer, Nadine [VerfasserIn] |
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| | Rapp, Felicitas [VerfasserIn] |
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| | Metzgeroth, Georgia [VerfasserIn] |
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| | Hecht, Anna [VerfasserIn] |
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| | Höger, Thomas [VerfasserIn] |
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| | Merz, Christian [VerfasserIn] |
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| | Hofmann, Wolf-Karsten [VerfasserIn] |
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| | Nolte, Florian [VerfasserIn] |
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| | Nowak, Daniel [VerfasserIn] |
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| Titel: | Treatment with the apoptosis inhibitor Asunercept reduces clone sizes in patients with lower risk Myelodysplastic Neoplasms |
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| Verf.angabe: | Alexander Streuer, Johann-Christoph Jann, Tobias Boch, Maximilian Mossner, Vladimir Riabov, Nanni Schmitt, Eva Altrock, Qingyu Xu, Marie Demmerle, Verena Nowak, Julia Oblaender, Iris Palme, Nadine Weimer, Felicitas Rapp, Georgia Metzgeroth, Anna Hecht, Thomas Höger, Christian Merz, Wolf-Karsten Hofmann, Florian Nolte, Daniel Nowak |
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| E-Jahr: | 2024 |
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| Jahr: | April 2024 |
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| Umfang: | 13 S. |
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| Fussnoten: | Online veröffentlicht: 27. Februar 2024 ; Gesehen am 03.02.2025 |
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| Titel Quelle: | Enthalten in: Annals of hematology |
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| Ort Quelle: | Berlin : Springer, 1991 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 103(2024), 4 vom: Apr., Seite 1221-1233 |
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| ISSN Quelle: | 1432-0584 |
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| Abstract: | In low-risk Myelodysplastic Neoplasms (MDS), increased activity of apoptosis-promoting factors such as tumor necrosis factor (TNFα) and pro-apoptotic Fas ligand (CD95L) have been described as possible pathomechanisms leading to impaired erythropoiesis. Asunercept (APG101) is a novel therapeutic fusion protein blocking CD95, which has previously shown partial efficacy in reducing transfusion requirement in a clinical phase I trial for low-risk MDS patients (NCT01736436; 2012-11-26). In the current study we aimed to evaluate the effect of Asunercept therapy on the clonal bone marrow composition to identify potential biomarkers to predict response. Bone marrow samples of n = 12 low-risk MDS patients from the above referenced clinical trial were analyzed by serial deep whole exome sequencing in a total of n = 58 time points. We could distinguish a mean of 3.5 molecularly defined subclones per patient (range 2-6). We observed a molecular response defined as reductions of dominant clone sizes by a variant allele frequency (VAF) decrease of at least 10% (mean 20%, range: 10.5-39.2%) in dependency of Asunercept treatment in 9 of 12 (75%) patients. Most of this decline in clonal populations was observed after completion of 12 weeks treatment. Particularly early and pronounced reductions of clone sizes were found in subclones driven by mutations in genes involved in regulation of methylation (n = 1 DNMT3A, n = 1 IDH2, n = 1 TET2). Our results suggest that APG101 could be efficacious in reducing clone sizes of mutated hematopoietic cells in the bone marrow of Myelodysplastic Neoplasms, which warrants further investigation. |
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| DOI: | doi:10.1007/s00277-024-05664-5 |
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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.
kostenfrei: Volltext: https://doi.org/10.1007/s00277-024-05664-5 |
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| | kostenfrei: Volltext: http://link.springer.com/article/10.1007/s00277-024-05664-5 |
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| | DOI: https://doi.org/10.1007/s00277-024-05664-5 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1916183735 |
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| Verknüpfungen: | → Zeitschrift |
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Treatment with the apoptosis inhibitor Asunercept reduces clone sizes in patients with lower risk Myelodysplastic Neoplasms / Streuer, Alexander [VerfasserIn]; April 2024 (Online-Ressource)
