High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia
A partir d'échantillons de moelle osseuse prélevés sur 230 patients pédiatriques atteints d'une leucémie myéloïde aiguë, cette étude montre qu'un niveau élevé d'expression du facteur de transcription GATA2 est associé à un pronostic défavorable
In acute myeloid leukemia (AML), aberrant expression and mutations of transcription factors have been correlated with disease outcome. In de novo pediatric AML patients, we performed expression and mutation screening of GATA2, which is an essential transcription factor for regulation of myeloid lineage determination. GATA2 mutations were detected in 5/230 patients, representing a frequency of 2.2% overall, and 9.8% in cytogenetically normal AML. GATA2 expression analysis demonstrated that in 155/237 diagnostic samples (65%), GATA2 expression was higher than in normal bone marrow. In complete remission, normalization of GATA2 expression was observed, whereas GATA2 expression levels stayed high in patients with resistant disease. Importantly, high GATA2 expression at diagnosis was an independent poor prognostic factor for overall survival (HR 1.7, p=0.045), event free survival (HR 2.1, p=0.002), and disease free survival (HR 2.3, p=0.004). The prognostic impact of GATA2 was particularly evident in specific AML-subgroups. In patients with FAB-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.
Blood , résumé, 2012