Presence of FLT3-ITD and high BAALCexpression are independent prognostic markers in childhood acute myeloid leukemia

Mutation status of FLT3, NPM1, CEBPA, and WT1genes and gene expression levels of ERG, MN1, BAALC, FLT3, and WT1have been identified as possible prognostic markers in acute myeloid leukemia (AML). We have performed a thorough prognostic evaluation of these genetic markers in patients with pediatric AML enrolled in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) 1993 or NOPHO 2004 protocols. Mutation status and expression levels were analyzed in 185 and 149 patients, respectively. Presence of FLT3-internal tandem duplication (ITD) was associated with significantly inferior event-free survival (EFS), whereas presence of an NPM1mutation in the absence of FLT3-ITD correlated with significantly improved EFS. Furthermore, high levels of ERGand BAALCtranscripts were associated with inferior EFS. No significant correlation with survival was seen for mutations in CEBPAand WT1or with gene expression levels of MN1, FLT3, and WT1. In multivariate analysis, the presence of FLT3-ITD and high BAALCexpression were identified as independent prognostic markers of inferior EFS. We conclude that analysis of the mutational status of FLT3and NPM1at diagnosis is important for prognostic stratification of patients with pediatric AML and that determination of the BAALCgene expression level can add valuable information.