TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome
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- 1 March 2012
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 119 (9), 2114-2121
- https://doi.org/10.1182/blood-2011-08-375758
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.Keywords
This publication has 41 references indexed in Scilit:
- Identification of a Novel TP53 Cancer Susceptibility Mutation Through Whole-Genome Sequencing of a Patient With Therapy-Related AMLJAMA, 2011
- p53 loss promotes acute myeloid leukemia by enabling aberrant self-renewalGenes & Development, 2010
- Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progressionHaematologica, 2009
- TP53 mutations in myeloid malignancies are either homozygous or hemizygous due to copy number-neutral loss of heterozygosity or deletion of 17pLeukemia, 2009
- Circos: An information aesthetic for comparative genomicsGenome Research, 2009
- Benzene-Induced Hematopoietic Neoplasms Including Myeloid Leukemia in Trp53-Deficient C57BL/6 and C3H/He MiceToxicological Sciences, 2009
- Mutation inTET2in Myeloid CancersNew England Journal of Medicine, 2009
- Mouse models of human AML accurately predict chemotherapy responseGenes & Development, 2009
- Cytogenetic, Molecular Genetic, and Clinical Characteristics of Acute Myeloid Leukemia With a Complex KaryotypeSeminars in Oncology, 2008
- Overexpression of sPRDM16 coupled with loss of p53 induces myeloid leukemias in miceJCI Insight, 2007