GATA2 zinc finger 1 mutations are associated with distinct clinico-biological features and outcomes different from GATA2 zinc finger 2 mutations ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-09

AUTHORS

Feng-Ming Tien, Hsin-An Hou, Cheng-Hong Tsai, Jih-Luh Tang, Yu-Chiao Chiu, Chien-Yuan Chen, Yuan-Yeh Kuo, Mei-Hsuan Tseng, Yen-Ling Peng, Ming-Chih Liu, Chia-Wen Liu, Xiu-Wen Liao, Liang-In Lin, Chien-Ting Lin, Shang-Ju Wu, Bor-Sheng Ko, Szu-Chun Hsu, Shang-Yi Huang, Ming Yao, Wen-Chien Chou, Hwei-Fang Tien

ABSTRACT

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. More... »

PAGES

87

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41408-018-0123-2

    DOI

    http://dx.doi.org/10.1038/s41408-018-0123-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1106476020

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30190467


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