TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome

• Verfasst von: Rücker, Frank Gert [VerfasserIn]
• Verfasst von: Schlenk, Richard Friedrich [VerfasserIn]
• Verfasst von: Bullinger, Lars [VerfasserIn]
• Verfasst von: Zenz, Thorsten [VerfasserIn]
• Verfasst von: Ganser, Arnold [VerfasserIn]
• Verfasst von: Lichter, Peter [VerfasserIn]
• Verfasst von: Döhner, Konstanze [VerfasserIn]
• Verfasst von: Döhner, Hartmut [VerfasserIn]
• Titel: TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome
• Verf.angabe: Frank G. Rücker, Richard F. Schlenk, Lars Bullinger, Sabine Kayser, Veronica Teleanu, Helena Kett, Marianne Habdank, Carla-Maria Kugler, Karlheinz Holzmann, Verena I. Gaidzik, Peter Paschka, Gerhard Held, Marie von Lilienfeld-Toal, Michael Lübbert, Stefan Fröhling, Thorsten Zenz, Jürgen Krauter, Brigitte Schlegelberger, Arnold Ganser, Peter Lichter, Konstanze Döhner and Hartmut Döhner
• E-Jahr: 2012
• Jahr: March 2012
• Umfang: 8 S.
• Fussnoten: Prepublished online as Blood First Edition paper, December 20, 2011; DOI 10.1182/blood-2011-08-375758 ; Gesehen am 08.05.2018
• Titel Quelle: Enthalten in: Blood
• Ort Quelle: Washington, DC : American Society of Hematology, 1946
• Jahr Quelle: 2012
• Band/Heft Quelle: 119(2012), 9, Seite 2114-2121
• ISSN Quelle: 1528-0020
• DOI: doi:10.1182/blood-2011-08-375758
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1574274503

Abstract

To assess the frequency of TP53 alterations and their correlation with other genetic changes and outcome in acute myeloid leukemia with complex karyotype (CK-AML), we performed integrative analysis using TP53 mutational screening and array-based genomic profiling in 234 CK-AML. TP53 mutations were found in 141/234 (60%) and TP53 losses were identified in 94/234 (40%) CK-AML; in total, 164/234 (70%) cases had TP53 alterations. TP53-altered CK-AML were characterized by a higher degree of genomic complexity (aberrations per case, 14.30 vs. 6.16; P<.0001), and by a higher frequency of specific copy number alterations, such as -5/5q-, -7/7q-, -16/16q-, -18/18q-, +1/+1p, and +11/+11q/amp11q13~25; among CK-AML, TP53-altered more frequently exhibited a monosomal karyotype (MK). Patients with TP53 alterations were older and had significantly lower complete remission rates, inferior event-free, relapse-free, and overall survival. In multivariable analysis for overall survival, TP53 alterations, white blood cell counts, and age were the only significant factors. In conclusion, TP53 is the most frequently known altered gene in CK-AML. TP53 alterations are associated with older age, genomic complexity, specific DNA copy number alterations, MK, and dismal outcome. In multivariable analysis, TP53 alteration is the most important prognostic factor in CK-AML, outweighing all other variables, including the MK category.