High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia
Blood , Volume 120 - Issue 10 p. 2064- 2075
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.
|Organisation||Department of Immunology|
Luesink, M, Hollink, I.H.I.M, van der Velden, V.H.J, Knops, R.H.J.N, Boezeman, J.B.M, de Haas, V, … Jansen, J.H. (2012). High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia. Blood, 120(10), 2064–2075. doi:10.1182/blood-2011-12-397083