title: TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome.
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-AMLs. TP53 mutations were found in 141 of 234 (60%) and TP53 losses were identified in 94 of 234 (40%) CK-AMLs; in total, 164 of 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-AMLs, 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.
authors.affiliation: Department of Internal Medicine III, University Hospital of Ulm, Albert-Einstein-Allee 23, Ulm, Germany.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Rücker
authors.forename: Richard F
authors.initials: RF
authors.lastname: Schlenk
authors.forename: Lars
authors.initials: L
authors.lastname: Bullinger
authors.forename: Sabine
authors.initials: S
authors.lastname: Kayser
authors.forename: Veronica
authors.initials: V
authors.lastname: Teleanu
authors.forename: Helena
authors.initials: H
authors.lastname: Kett
authors.forename: Marianne
authors.initials: M
authors.lastname: Habdank
authors.forename: Carla-Maria
authors.initials: CM
authors.lastname: Kugler
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Holzmann
authors.forename: Verena I
authors.initials: VI
authors.lastname: Gaidzik
authors.forename: Peter
authors.initials: P
authors.lastname: Paschka
authors.forename: Gerhard
authors.initials: G
authors.lastname: Held
authors.forename: Marie
authors.initials: M
authors.lastname: von Lilienfeld-Toal
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
authors.forename: Stefan
authors.initials: S
authors.lastname: Fröhling
authors.forename: Thorsten
authors.initials: T
authors.lastname: Zenz
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauter
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Konstanze
authors.initials: K
authors.lastname: Döhner
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: D016159:Tumor Suppressor Protein p53