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| Verfasst von: | Jahn, Nikolaus [VerfasserIn]  |
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| | Terzer, Tobias [VerfasserIn] |
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| | Sträng, Eric [VerfasserIn] |
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| | Dolnik, Anna [VerfasserIn] |
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| | Cocciardi, Sibylle [VerfasserIn] |
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| | Panina, Ekaterina [VerfasserIn] |
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| | Corbacioglu, Andrea [VerfasserIn] |
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| | Herzig, Julia [VerfasserIn] |
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| | Weber, Daniela [VerfasserIn] |
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| | Schrade, Anika [VerfasserIn] |
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| | Götze, Katharina [VerfasserIn] |
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| | Schröder, Thomas [VerfasserIn] |
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| | Lübbert, Michael [VerfasserIn] |
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| | Wellnitz, Dominique [VerfasserIn] |
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| | Koller, Elisabeth [VerfasserIn] |
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| | Schlenk, Richard Friedrich [VerfasserIn] |
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| | Gaidzik, Verena I. [VerfasserIn] |
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| | Paschka, Peter [VerfasserIn] |
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| | Rücker, Frank G. [VerfasserIn] |
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| | Heuser, Michael [VerfasserIn] |
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| | Thol, Felicitas [VerfasserIn] |
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| | Ganser, Arnold [VerfasserIn] |
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| | Benner, Axel [VerfasserIn] |
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| | Döhner, Hartmut [VerfasserIn] |
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| | Bullinger, Lars [VerfasserIn] |
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| | Döhner, Konstanze [VerfasserIn] |
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| Titel: | Genomic heterogeneity in core-binding factor acute myeloid leukemia and its clinical implication |
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| Verf.angabe: | Nikolaus Jahn, Tobias Terzer, Eric Sträng, Anna Dolnik, Sibylle Cocciardi, Ekaterina Panina, Andrea Corbacioglu, Julia Herzig, Daniela Weber, Anika Schrade, Katharina Götze, Thomas Schröder, Michael Lübbert, Dominique Wellnitz, Elisabeth Koller, Richard F. Schlenk, Verena I. Gaidzik, Peter Paschka, Frank G. Rücker, Michael Heuser, Felicitas Thol, Arnold Ganser, Axel Benner, Hartmut Döhner, Lars Bullinger, and Konstanze Döhner |
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| E-Jahr: | 2020 |
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| Jahr: | 21 December 2020 |
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| Umfang: | 11 S. |
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| Fussnoten: | Gesehen am 10.03.2022 |
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| Titel Quelle: | Enthalten in: Blood advances |
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| Ort Quelle: | Washington, DC : American Society of Hematology, 2016 |
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| Jahr Quelle: | 2020 |
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| Band/Heft Quelle: | 4(2020), 24, Seite 6342-6352 |
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| ISSN Quelle: | 2473-9537 |
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| Abstract: | Core-binding factor (CBF) acute myeloid leukemia (AML) encompasses AML with inv(16)(p13.1q22) and AML with t(8;21)(q22;q22.1). Despite sharing a common pathogenic mechanism involving rearrangements of the CBF transcriptional complex, there is growing evidence for considerable genotypic heterogeneity. We comprehensively characterized the mutational landscape of 350 adult CBF-AML [inv(16): n = 160, t(8;21): n = 190] performing targeted sequencing of 230 myeloid cancer-associated genes. Apart from common mutations in signaling genes, mainly NRAS, KIT, and FLT3, both CBF-AML entities demonstrated a remarkably diverse pattern with respect to the underlying cooperating molecular events, in particular in genes encoding for epigenetic modifiers and the cohesin complex. In addition, recurrent mutations in novel collaborating candidate genes such as SRCAP (5% overall) and DNM2 (6% of t(8;21) AML) were identified. Moreover, aberrations altering transcription and differentiation occurred at earlier leukemic stages and preceded mutations impairing proliferation. Lasso-penalized models revealed an inferior prognosis for t(8;21) AML, trisomy 8, as well as FLT3 and KIT exon 17 mutations, whereas NRAS and WT1 mutations conferred superior prognosis. Interestingly, clonal heterogeneity was associated with a favorable prognosis. When entering mutations by functional groups in the model, mutations in genes of the methylation group (ie, DNMT3A, TET2) had a strong negative prognostic impact. |
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| DOI: | doi:10.1182/bloodadvances.2020002673 |
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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/bloodadvances.2020002673 |
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| | DOI: https://doi.org/10.1182/bloodadvances.2020002673 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1788500334 |
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| Verknüpfungen: | → Zeitschrift |
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Genomic heterogeneity in core-binding factor acute myeloid leukemia and its clinical implication / Jahn, Nikolaus [VerfasserIn]; 21 December 2020 (Online-Ressource)
