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| Verfasst von: | Marcucci, Guido [VerfasserIn]  |
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| | Yan, Pearlly [VerfasserIn] |
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| | Maharry, Kati [VerfasserIn] |
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| | Frankhouser, David [VerfasserIn] |
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| | Nicolet, Deedra [VerfasserIn] |
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| | Metzeler, Klaus H. [VerfasserIn] |
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| | Kohlschmidt, Jessica [VerfasserIn] |
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| | Mrózek, Krzysztof [VerfasserIn] |
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| | Wu, Yue-Zhong [VerfasserIn] |
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| | Bucci, Donna [VerfasserIn] |
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| | Curfman, John P. [VerfasserIn] |
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| | Whitman, Susan P. [VerfasserIn] |
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| | Eisfeld, Ann-Kathrin [VerfasserIn] |
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| | Mendler, Jason H. [VerfasserIn] |
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| | Schwind, Sebastian [VerfasserIn] |
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| | Becker, Heiko [VerfasserIn] |
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| | Bär, Constance [VerfasserIn] |
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| | Carroll, Andrew J. [VerfasserIn] |
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| | Baer, Maria R. [VerfasserIn] |
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| | Wetzler, Meir [VerfasserIn] |
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| | Carter, Thomas H. [VerfasserIn] |
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| | Powell, Bayard L. [VerfasserIn] |
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| | Kolitz, Jonathan E. [VerfasserIn] |
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| | Byrd, John C. [VerfasserIn] |
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| | Plass, Christoph [VerfasserIn] |
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| | Garzon, Ramiro [VerfasserIn] |
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| | Caligiuri, Michael A. [VerfasserIn] |
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| | Stone, Richard M. [VerfasserIn] |
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| | Volinia, Stefano [VerfasserIn] |
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| | Bundschuh, Ralf [VerfasserIn] |
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| | Bloomfield, Clara D. [VerfasserIn] |
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| Titel: | Epigenetics meets genetics in acute myeloid leukemia |
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| Titelzusatz: | clinical impact of a novel seven-gene score |
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| Verf.angabe: | Guido Marcucci, Pearlly Yan, Kati Maharry, David Frankhouser, Deedra Nicolet, Klaus H. Metzeler, Jessica Kohlschmidt, Krzysztof Mrózek, Yue-Zhong Wu, Donna Bucci, John P. Curfman, Susan P. Whitman, Ann-Kathrin Eisfeld, Jason H. Mendler, Sebastian Schwind, Heiko Becker, Constance Bär, Andrew J. Carroll, Maria R. Baer, Meir Wetzler, Thomas H. Carter, Bayard L. Powell, Jonathan E. Kolitz, John C. Byrd, Christoph Plass, Ramiro Garzon, Michael A. Caligiuri, Richard M. Stone, Stefano Volinia, Ralf Bundschuh, and Clara D. Bloomfield |
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| E-Jahr: | 2014 |
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| Jahr: | February 20, 2014 |
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| Umfang: | 9 S. |
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| Teil: | volume:32 |
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| | year:2014 |
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| | number:6 |
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| | pages:548-556 |
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| | extent:9 |
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| Fussnoten: | Published online ahead of print at www.jco.org on December 30, 2013 ; Gesehen am 22.06.2021 |
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| Titel Quelle: | Enthalten in: Journal of clinical oncology |
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| Ort Quelle: | Alexandria, Va. : American Society of Clinical Oncology, 1983 |
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| Jahr Quelle: | 2014 |
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| Band/Heft Quelle: | 32(2014), 6, Seite 548-556 |
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| ISSN Quelle: | 1527-7755 |
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| Abstract: | Purpose Molecular risk stratification of acute myeloid leukemia (AML) is largely based on genetic markers. However, epigenetic changes, including DNA methylation, deregulate gene expression and may also have prognostic impact. We evaluated the clinical relevance of integrating DNA methylation and genetic information in AML. Methods Next-generation sequencing analysis of methylated DNA identified differentially methylated regions (DMRs) associated with prognostic mutations in older (≥ 60 years) cytogenetically normal (CN) patients with AML (n = 134). Genes with promoter DMRs and expression levels significantly associated with outcome were used to compute a prognostic gene expression weighted summary score that was tested and validated in four independent patient sets (n = 355). Results In the training set, we identified seven genes (CD34, RHOC, SCRN1, F2RL1, FAM92A1, MIR155HG, and VWA8) with promoter DMRs and expression associated with overall survival (OS; P ≤ .001). Each gene had high DMR methylation and lower expression, which were associated with better outcome. A weighted summary expression score of the seven gene expression levels was computed. A low score was associated with a higher complete remission (CR) rate and longer disease-free survival and OS (P < .001 for all end points). This was validated in multivariable models and in two younger (< 60 years) and two older independent sets of patients with CN-AML. Considering the seven genes individually, the fewer the genes with high expression, the better the outcome. Younger and older patients with no genes or one gene with high expression had the best outcomes (CR rate, 94% and 87%, respectively; 3-year OS, 80% and 42%, respectively). Conclusion A seven-gene score encompassing epigenetic and genetic prognostic information identifies novel AML subsets that are meaningful for treatment guidance. |
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| DOI: | doi:10.1200/JCO.2013.50.6337 |
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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 ; Verlag: https://doi.org/10.1200/JCO.2013.50.6337 |
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| | Volltext: https://ascopubs.org/doi/10.1200/JCO.2013.50.6337 |
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| | DOI: https://doi.org/10.1200/JCO.2013.50.6337 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1761039326 |
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| Verknüpfungen: | → Zeitschrift |
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Epigenetics meets genetics in acute myeloid leukemia / Marcucci, Guido [VerfasserIn]; February 20, 2014 (Online-Ressource)
