title: GATA2 mutations in patients with acute myeloid leukemia-paired samples analyses show that the mutation is unstable during disease evolution.
abstract: Recently, mutations of the GATA binding protein 2 (GATA2) gene were identified in acute myeloid leukemia (AML) patients with CEBPA double mutations (CEBPA (double-mut)), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, 14 different missense GATA2 mutations, which were all clustered in the highly conserved N-terminal zinc finger 1 domain, were identified in 27.4, 6.7, and 1 % of patients with CEBPA (double-mut), CEBPA (single-mut), and CEBPA wild type, respectively. All but one patient with GATA2 mutation had concurrent CEBPA mutation. GATA2 mutations were closely associated with younger age, FAB M1 subtype, intermediate-risk cytogenetics, expression of HLA-DR, CD7, CD15, or CD34 on leukemic cells, and CEBPA mutation, but negatively associated with FAB M4 subtype, favorable-risk cytogenetics, and NPM1 mutation. Patients with GATA2 mutation had significantly better overall survival and relapse-free survival than those without GATA2 mutation. Sequential analysis showed that the original GATA2 mutations might be lost during disease progression in GATA2-mutated patients, while novel GATA2 mutations might be acquired at relapse in GATA2-wild patients. In conclusion, AML patients with GATA2 mutations had distinct clinic-biological features and a favorable prognosis. GATA2 mutations might be lost or acquired at disease progression, implying that it was a second hit in the leukemogenesis of AML, especially those with CEBPA mutation.
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Hou
authors.forename: Yun-Chu
authors.initials: YC
authors.lastname: Lin
authors.forename: Yuan-Yeh
authors.initials: YY
authors.lastname: Kuo
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Chou
authors.forename: Chien-Chin
authors.initials: CC
authors.lastname: Lin
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Liu
authors.forename: Chien-Yuan
authors.initials: CY
authors.lastname: Chen
authors.forename: Liang-In
authors.initials: LI
authors.lastname: Lin
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Tseng
authors.forename: Chi-Fei
authors.initials: CF
authors.lastname: Huang
authors.forename: Ying-Chieh
authors.initials: YC
authors.lastname: Chiang
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Liu
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Liu
authors.forename: Jih-Luh
authors.initials: JL
authors.lastname: Tang
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Shang-Yi
authors.initials: SY
authors.lastname: Huang
authors.forename: Bor-Sheng
authors.initials: BS
authors.lastname: Ko
authors.forename: Szu-Chun
authors.initials: SC
authors.lastname: Hsu
authors.forename: Shang-Ju
authors.initials: SJ
authors.lastname: Wu
authors.forename: Woei
authors.initials: W
authors.lastname: Tsay
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Hwei-Fang
authors.initials: HF
authors.lastname: Tien
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D002869:Chromosome Aberrations; D018450:Disease Progression; D005500:Follow-Up Studies; D050989:GATA2 Transcription Factor / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D059785:Karyotype; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D000090243:Nucleophosmin; D011379:Prognosis; D055815:Young Adult
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; C000716967:NPM1 protein, human; D000090243:Nucleophosmin