Full-length mutation search of the TP53 gene in acute myeloid leukemia has increased significance as a prognostic factor
Full-length mutation search of the TP53 gene in acute myeloid leukemia has increased significance as a prognostic factor
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DOI：
10.1007/s00277-017-3143-2
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发表时间：
2017
影响因子：
3.5
通讯作者：
K. Terada;H. Yamaguchi;T. Ueki;K. Usuki;Yutaka Kobayashi;K. Tajika;S. Gomi;S. Kurosawa;Keiki Miyadera;Taichiro Tokura;Ikuko Omori;Atushi Marumo;Y. Fujiwara;Shunsuke Yui;Takeshi Ryotokuji;Y. Osaki;Kunihito Arai;T. Kitano;F. Kosaka;S. Wakita;H. Tamai;T. Fukuda;K. Inokuchi
中科院分区：
文献类型：
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作者：
K. Terada;H. Yamaguchi;T. Ueki;K. Usuki;Yutaka Kobayashi;K. Tajika;S. Gomi;S. Kurosawa;Keiki Miyadera;Taichiro Tokura;Ikuko Omori;Atushi Marumo;Y. Fujiwara;Shunsuke Yui;Takeshi Ryotokuji;Y. Osaki;Kunihito Arai;T. Kitano;F. Kosaka;S. Wakita;H. Tamai;T. Fukuda;K. Inokuchi
据报道，TP53基因异常是急性髓系白血病（AML）的不利预后因素。然而，到目前为止，几乎所有TP53基因异常的研究都仅限于DNA结合域的突变搜索。由于目前对TP53基因全长突变和缺失进行检测的报道很少，因此TP53基因异常的临床特征尚未明确。本研究中，412例新发AML病例中，7.3%出现TP53基因突变（30例中有33个突变），8例（27%）出现DNA结合域外突变。358例中有3.1%出现TP53基因缺失。所有病例均存在单等位基因缺失，并伴有相反等位基因上的 TP53 基因突变。多变量分析表明，DNA结合域内和DNA结合域外的TP53基因突变是整个队列中总生存和无复发生存的独立不良预后因素，也是70岁及以下细胞遗传学预后中等的FLT3-ITD阴性AML病例的不利预后因素。因此，在分层治疗中，全长寻找TP53基因突变非常重要。
TP53gene abnormality has been reported to be an unfavorable prognostic factor in acute myeloid leukemia (AML). However, almost all studies ofTP53gene abnormality so far have been limited to mutation searches in the DNA binding domain. As there have been few reports examining both mutation and deletion over the full-length of theTP53gene, the clinical characteristics ofTP53gene abnormality have not yet been clearly established. In this study,TP53gene mutation was observed in 7.3% of the total 412 de novo AML cases (33 mutations in 30 cases), with mutation outside the DNA binding domain in eight cases (27%).TP53gene deletion was observed in 3.1% of 358 cases. All cases had monoallelic deletion withTP53gene mutation on the opposite allele. Multivariate analysis demonstrated thatTP53gene mutation in the DNA binding domain and outside the DNA binding domain was an independent poor prognostic factor for overall survival and relapse-free survival among the total cohort and it is also an unfavorable prognostic factor inFLT3-ITD-negative AML cases aged 70 years or below with intermediate cytogenetic prognosis. In stratified treatment, full-length search forTP53gene mutation is therefore very important.