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| Verfasst von: | Riabov, Vladimir [VerfasserIn]  |
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| | Xu, Qingyu [VerfasserIn] |
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| | Schmitt, Nanni [VerfasserIn] |
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| | Streuer, Alexander [VerfasserIn] |
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| | Ge, Guo [VerfasserIn] |
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| | Bolanos, Lyndsey [VerfasserIn] |
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| | Wunderlich, Mark [VerfasserIn] |
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| | Jann, Johann-Christoph [VerfasserIn] |
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| | Wein, Alina [VerfasserIn] |
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| | Altrock, Eva [VerfasserIn] |
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| | Demmerle, Marie [VerfasserIn] |
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| | Mukherjee, Sanjay [VerfasserIn] |
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| | Ali, Abdullah Mahmood [VerfasserIn] |
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| | Rapp, Felicitas [VerfasserIn] |
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| | Nowak, Verena [VerfasserIn] |
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| | Weimer, Nadine [VerfasserIn] |
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| | Obländer, Julia [VerfasserIn] |
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| | Palme, Iris [VerfasserIn] |
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| | Göl, Melda [VerfasserIn] |
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| | Jawhar, Ahmed [VerfasserIn] |
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| | Darwich, Ali [VerfasserIn] |
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| | Wuchter, Patrick [VerfasserIn] |
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| | Weiß, Christel [VerfasserIn] |
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| | Raza, Azra [VerfasserIn] |
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| | Foulks, Jason M. [VerfasserIn] |
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| | Starczynowski, Daniel T. [VerfasserIn] |
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| | Yang, Feng-Chun [VerfasserIn] |
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| | Metzgeroth, Georgia [VerfasserIn] |
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| | Steiner, Laurenz [VerfasserIn] |
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| | Jawhar, Mohamad [VerfasserIn] |
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| | Hofmann, Wolf-Karsten [VerfasserIn] |
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| | Nowak, Daniel [VerfasserIn] |
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| Titel: | ASXL1 mutations are associated with a response to alvocidib and 5-azacytidine combination in myelodysplastic neoplasms |
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| Verf.angabe: | Vladimir Riabov, Qingyu Xu, Nanni Schmitt, Alexander Streuer, Guo Ge, Lyndsey Bolanos, Mark Wunderlich, Johann-Christoph Jann, Alina Wein, Eva Altrock, Marie Demmerle, Sanjay Mukherjee, Abdullah Mahmood Ali, Felicitas Rapp, Verena Nowak, Nadine Weimer, Julia Obländer, Iris Palme, Melda Göl, Ahmed Jawhar, Ali Darwich, Patrick Wuchter, Christel Weiss, Azra Raza, Jason M. Foulks, Daniel T. Starczynowski, Feng-Chun Yang, Georgia Metzgeroth, Laurenz Steiner, Mohamad Jawhar, Wolf-Karsten Hofmann, Daniel Nowak |
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| E-Jahr: | 2024 |
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| Jahr: | May, 2024 |
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| Umfang: | 13 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Online verfügbar: 2. November, 2023 ; Gesehen am 26.02.2025 |
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| Titel Quelle: | Enthalten in: Haematologica |
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| Ort Quelle: | Pavia : Ferrata Storti Foundation, 2014 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 109(2024), 5, Seite 1426-1438 |
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| ISSN Quelle: | 1592-8721 |
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| Abstract: | Inhibitors of anti-apoptotic BCL-2 family proteins in combination with chemotherapy and hypomethylating agents (HMA) are promising therapeutic approaches in acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). Alvocidib, a cyclin-dependent kinase 9 (CDK9) inhibitor and indirect transcriptional repressor of the anti-apoptotic factor MCL-1, has previously shown clinical activity in AML. Availability of biomarkers for response to the alvocidib + 5-azacytidine (5-AZA) could also extend the rationale of this treatment concept to high-risk MDS. In this study, we performed a comprehensive in vitro assessment of alvocidib and 5-AZA effects in N=45 high-risk MDS patients. Our data revealed additive cytotoxic effects of the combination treatment. Mutational profiling of MDS samples identified ASXL1 mutations as predictors of response. Further, increased response rates were associated with higher gene expression of the pro-apoptotic factor NOXA in ASXL1-mutated samples. The higher sensitivity of ASXL1 mutant cells to the combination treatment was confirmed in vivo in ASXL1Y588X transgenic mice. Overall, our study demonstrated augmented activity for the alvocidib + 5-AZA combination in higher-risk MDS and identified ASXL1 mutations as a biomarker of response for potential stratification studies. |
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| DOI: | doi:10.3324/haematol.2023.282921 |
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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/10.3324/haematol.2023.282921 |
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| | Volltext: https://haematologica.org/article/view/haematol.2023.282921 |
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| | DOI: https://doi.org/10.3324/haematol.2023.282921 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1918592829 |
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| Verknüpfungen: | → Zeitschrift |
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ASXL1 mutations are associated with a response to alvocidib and 5-azacytidine combination in myelodysplastic neoplasms / Riabov, Vladimir [VerfasserIn]; May, 2024 (Online-Ressource)
