|Title:||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||Authors:||Tien, Feng-Ming
|Issue Date:||2018||Journal Volume:||8||Journal Issue:||9||Start page/Pages:||87||Source:||Blood Cancer Journal||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 (CEBPA double-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 CEBPA double-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. ? 2018, The Author(s).
|URI:||https://scholars.lib.ntu.edu.tw/handle/123456789/456666||ISSN:||2044-5385||DOI:||10.1038/s41408-018-0123-2||metadata.dc.subject.other:||ASXL1 protein; CCAAT enhancer binding protein alpha; DNA methyltransferase 3A; Flt3 ligand; isocitrate dehydrogenase 1; isocitrate dehydrogenase 2; K ras protein; mixed lineage leukemia protein; nucleophosmin; protein; protein p53; protein tyrosine phosphatase SHP 2; Ras protein; SF3B1 protein; SRSF2 protein; TET2 protein; transcription factor ETV6; transcription factor GATA 2; transcription factor RUNX1; U2AF1 protein; unclassified drug; WT1 protein; zinc finger protein; antineoplastic agent; transcription factor GATA 2; tumor marker; zinc finger protein; acute myeloid leukemia; adult; aged; Article; cancer prognosis; cancer survival; clinical feature; cohort analysis; cytogenetics; disease association; disease free survival; female; gene expression profiling; gene mutation; genetic association; human; karyotype; major clinical study; male; outcome assessment; overall survival; sequential analysis; treatment response; very elderly; young adult; acute myeloid leukemia; biology; cancer grading; cancer staging; chemistry; dna mutational analysis; exon; genetics; Kaplan Meier method; middle aged; molecular genetics; mortality; mutation; pathology; procedures; prognosis; protein domain; single nucleotide polymorphism; treatment outcome; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Computational Biology; DNA Mutational Analysis; Exons; Female; GATA2 Transcription Factor; Humans; Kaplan-Meier Estimate; Karyotype; Leukemia, Myeloid, Acute; Male; Middle Aged; Molecular Sequence Annotation; Mutation; Neoplasm Grading; Neoplasm Staging; Polymorphism, Single Nucleotide; Prognosis; Protein Interaction Domains and Motifs; Treatment Outcome; Young Adult; Zinc Fingers
|Appears in Collections:||生物科技研究所|
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