High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia.
In acute myeloid leukemia (AML), aberrant expression and mutations of transcription factors have been correlated with disease outcome. In the present study, we performed expression and mutation screening of GATA2, which is an essential transcription factor for regulation of myeloid lineage determination, in de novo pediatric AML patients. GATA2 mutations were detected in 5 of 230 patients, representing a frequency of 2.2% overall and 9.8% in cytogenetically normal AML. GATA2 expression analysis demonstrated that in 155 of 237 diagnostic samples (65%), GATA2 expression was higher than in normal BM. In complete remission, normalization of GATA2 expression was observed, whereas GATA2 expression levels stayed high in patients with resistant disease. High GATA2 expression at diagnosis was an independent poor prognostic factor for overall survival (hazard ratio [HR] = 1.7, P = .045), event-free survival (HR = 2.1, P = .002), and disease-free survival (HR = 2.3, P = .004). The prognostic impact of GATA2 was particularly evident in specific AML subgroups. In patients with French-American-British M5 morphology, inv(16), or high WT1 expression, significant differences in survival were observed between patients with high versus normal GATA2 expression. We conclude that high GATA2 expression is a novel poor prognostic marker in pediatric AML, which may contribute to better risk-group stratification and risk-adapted therapy in the future.
Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
Maaike
M
Luesink
Iris H I M
IH
Hollink
Vincent H J
VH
van der Velden
Ruth H J N
RH
Knops
Jan B M
JB
Boezeman
Valérie
V
de Haas
Jan
J
Trka
Andre
A
Baruchel
Dirk
D
Reinhardt
Bert A
BA
van der Reijden
Marry M
MM
van den Heuvel-Eibrink
C Michel
CM
Zwaan
Joop H
JH
Jansen
D002648:Child; D002675:Child, Preschool; D005260:Female; D050989:GATA2 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D016896:Treatment Outcome; D025721:WT1 Proteins / Q000235:genetics; D044465:White People
D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D015514:Oncogene Proteins, Fusion; D025721:WT1 Proteins; C471254:inv(16) fusion protein, human