TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome
TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome
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DOI：
10.1182/blood-2011-08-375758
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发表时间：
2012-03-01
期刊：
影响因子：
20.3
通讯作者：
Doehner, Hartmut
中科院分区：
文献类型：
--
作者：
Rueckner, Frank G.;Schlenk, Richard F.;Doehner, Hartmut
为了评估复杂核型急性髓系白血病（CK-AML）中TP 53改变的频率及其与其他遗传变化和结局的相关性，我们使用TP 53突变筛查和基于阵列的基因组分析对234例CK-AML进行了综合分析。234例CK-AML中有141例（60%）发现TP 53突变，94例（40%）发现TP 53缺失;总共234例病例中有164例（70%）存在TP 53改变。TP 53-改变的CK-AML的特征在于更高程度的基因组复杂性，（每例畸变率为14.30 vs 6.16; P <0.0001）和更高频率的特异性拷贝数改变，如-5/5q-、-7/7q-、-16/16q-、-18/18q-、+1/+1p和+11/+11q/amp11q13类似于25;在CK-AML中，TP 53改变更常见的是单体核型（MK）。TP 53基因改变的患者年龄较大，完全缓解率、无不良事件、无复发率和总生存率显著较低。在总生存率的多变量分析中，TP 53改变、白色血细胞计数和年龄是仅有的显著因素。总之，TP 53是CK-AML中最常见的已知改变基因。TP 53变异与年龄较大、基因组复杂性、特定DNA拷贝数变异、MK和不良结局相关。在多变量分析中，TP 53改变是CK-AML中最重要的预后因素，超过所有其他变量，包括MK类别。（血。2012; 119（9）：2114-2121）
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 similar to 25; among CK-AMLs, TP53altered 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. (Blood. 2012; 119(9): 2114-2121)