title: Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia.
abstract: Mutation status of FLT3, NPM1, CEBPA, and WT1 genes and gene expression levels of ERG, MN1, BAALC, FLT3, and WT1 have 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 NPM1 mutation in the absence of FLT3-ITD correlated with significantly improved EFS. Furthermore, high levels of ERG and BAALC transcripts were associated with inferior EFS. No significant correlation with survival was seen for mutations in CEBPA and WT1 or with gene expression levels of MN1, FLT3, and WT1. In multivariate analysis, the presence of FLT3-ITD and high BAALC expression were identified as independent prognostic markers of inferior EFS. We conclude that analysis of the mutational status of FLT3 and NPM1 at diagnosis is important for prognostic stratification of patients with pediatric AML and that determination of the BAALC gene expression level can add valuable information.
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Staffas
authors.forename: Meena
authors.initials: M
authors.lastname: Kanduri
authors.forename: Randi
authors.initials: R
authors.lastname: Hovland
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
authors.forename: Hans Beier
authors.initials: HB
authors.lastname: Ommen
authors.forename: Jonas
authors.initials: J
authors.lastname: Abrahamsson
authors.forename: Erik
authors.initials: E
authors.lastname: Forestier
authors.forename: Kirsi
authors.initials: K
authors.lastname: Jahnukainen
authors.forename: Ólafur G
authors.initials: ÓG
authors.lastname: Jónsson
authors.forename: Bernward
authors.initials: B
authors.lastname: Zeller
authors.forename: Josefine
authors.initials: J
authors.lastname: Palle
authors.forename: Gudmar
authors.initials: G
authors.lastname: Lönnerholm
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasle
authors.forename: Lars
authors.initials: L
authors.lastname: Palmqvist
authors.forename: Hans
authors.initials: H
authors.lastname: Ehrencrona
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D014408:Biomarkers, Tumor / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D020080:Tandem Repeat Sequences / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C442828:BAALC protein, human; D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3