文章：

TP53突变在新发急性髓系白血病患者中的研究：纵向随访显示该突变在疾病演变过程中保持稳定

TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution

原文发布日期：2015-07-31

DOI: 10.1038/bcj.2015.59

类型: Original Article

开放获取: 是

英文摘要：

The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.

摘要翻译： 

TP53突变在复杂核型（CK）急性髓系白血病（AML）患者中常见检出，但其在临床病程中的稳定性尚不明确。本研究在500例新发AML患者中发现7%存在TP53突变，其中CK患者突变率达58.8%。TP53突变与高龄、较低白细胞/血小板计数、FAB-M6亚型、不良风险细胞遗传学和CK显著相关，而与NPM1突变、FLT3/ITD及DNMT3A突变呈负相关。多因素分析证实，TP53突变是整体队列及CK亚组患者总生存期和无病生存期的独立不良预后因素。结合TP53突变与年龄、白细胞计数、细胞遗传学等9项预后因素构建的评分系统，能有效实现AML患者危险分层。对420份样本的序贯研究显示，TP53突变在AML进展中保持稳定，仅1例治疗相关AML（源自不同克隆）的126例TP53野生型患者出现了突变获得。结论：TP53突变与新发AML患者独特的临床生物学特征及不良预后相关，且在疾病进展中保持高度稳定性。

原文链接：

TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution