High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia

Maaike Luesink, Iris H.I.M. Hollink, Vincent H.J. Van Der Velden, Ruth H.J.N. Knops, Jan B.M. Boezeman, Valérie De Haas, Jan Trka, Andre Baruchel, Dirk Reinhardt, Bert A. Van Der Reijden, Marry M. Van Den Heuvel-Eibrink, C. Michel Zwaan, Joop H. Jansen

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

56 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)2064-2075
Aantal pagina's12
TijdschriftBlood
Volume120
Nummer van het tijdschrift10
DOI's
StatusGepubliceerd - 6 sep. 2012
Extern gepubliceerdJa

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