文章：

GATA2锌指1突变与成人急性髓系白血病中不同于GATA2锌指2突变的独特临床生物学特征和结局相关

GATA2 zinc finger 1 mutations are associated with distinct clinico-biological features and outcomes different from GATA2 zinc finger 2 mutations in adult acute myeloid leukemia

原文发布日期：2018-08-31

DOI: 10.1038/s41408-018-0123-2

类型: Article

开放获取: 是

英文摘要：

Mutations of the GATA binding protein 2 (GATA2) gene in myeloid malignancies usually cluster in the zinc finger 1 (ZF1) and the ZF2 domains. Mutations in different locations of GATA2 may have distinct impact on clinico-biological features and outcomes in AML patients, but little is known in this aspect. In this study, we explored GATA2 mutations in 693 de novo non-M3 AML patients and identified 44 GATA2 mutations in 43 (6.2%) patients, including 31 in ZF1, 10 in ZF2, and three outside the two domains. Different from GATA2 ZF2 mutations, ZF1 mutations were closely associated with French-American-British (FAB) M1 subtype, CEBPA double mutations (CEBPAdouble-mut), but inversely correlated with FAB M4 subtype, NPM1 mutations, and FLT3-ITD. ZF1-mutated AML patients had a significantly longer overall survival (OS) than GATA2-wild patients and ZF2-mutated patients in total cohort as well as in those with intermediate-risk cytogenetics and normal karyotype. ZF1 mutations also predicted better disease-free survival and a trend of better OS in CEBPAdouble-mut patients. Sequential analysis showed GATA2 mutations could be acquired at relapse. In conclusion, GATA2 ZF1 mutations are associated with distinct clinico-biological features and predict better prognosis, different from ZF2 mutations, in AML patients.

摘要翻译： 

髓系恶性肿瘤中GATA结合蛋白2（GATA2）基因的突变通常聚集在锌指1（ZF1）和ZF2结构域。GATA2不同位置的突变可能对AML患者的临床生物学特征和结局产生不同影响，但在这方面知之甚少。本研究在693例新发非M3型AML患者中探讨GATA2突变，共在43例（6.2%）患者中鉴定出44个GATA2突变，其中31个位于ZF1结构域，10个位于ZF2结构域，三个位于这两个结构域之外。与GATA2 ZF2突变不同，ZF1突变与法美英（FAB）分型M1亚型、CEBPA双突变密切相关，但与FAB M4亚型、NPM1突变和FLT3-ITD呈负相关。在整个队列中，以及在中危细胞遗传学和正常核型患者中，ZF1突变AML患者的总生存期均显著长于GATA2野生型患者和ZF2突变患者。在CEBPA双突变患者中，ZF1突变也预示着更好的无病生存期和更佳总生存期的趋势。序贯分析显示GATA2突变可在复发时获得。综上所述，在AML患者中，GATA2 ZF1突变与独特的临床生物学特征相关，并预示更好的预后，这与ZF2突变不同。

原文链接：

GATA2 zinc finger 1 mutations are associated with distinct clinico-biological features and outcomes different from GATA2 zinc finger 2 mutations in adult acute myeloid leukemia