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.

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.

• 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
• Journal: Blood cancer journal (Blood Cancer J) Vol. 8 Issue 9 Pg. 87 (08 31 2018) ISSN: 2044-5385 [Electronic] United States
• PMID: 30190467 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• GATA2 Transcription Factor
• NPM1 protein, human
• Nucleophosmin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Biomarkers, Tumor
• Computational Biology (methods)
• DNA Mutational Analysis
• Exons
• Female
• GATA2 Transcription Factor (chemistry, genetics)
• Humans
• Kaplan-Meier Estimate
• Karyotype
• Leukemia, Myeloid, Acute (genetics, mortality, pathology, therapy)
• Male
• Middle Aged
• Molecular Sequence Annotation
• Mutation
• Neoplasm Grading
• Neoplasm Staging
• Nucleophosmin
• Polymorphism, Single Nucleotide
• Prognosis
• Protein Interaction Domains and Motifs (genetics)
• Treatment Outcome
• Young Adult
• Zinc Fingers (genetics)