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

Staffas, Anna; Kanduri, Meena; Hovland, Randi; Rosenquist, Richard; Ommen, Hans Beier; Abrahamsson, Jonas; Forestier, Erik; Jahnukainen, Kirsi; Jonsson, Olafur G. and Zeller, Bernward, et al. (2011) In Blood 118(22). p.5905-5913
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... (More)
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. (Blood. 2011;118(22):5905-5913) (Less)
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Blood
volume
118
issue
22
pages
5905 - 5913
publisher
American Society of Hematology
external identifiers
  • wos:000297576600031
  • scopus:82155183329
ISSN
1528-0020
DOI
10.1182/blood-2011-05-353185
language
English
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yes
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0f18013d-7546-4ee5-8d12-f625869a2471 (old id 2292033)
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2012-01-11 08:53:25
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2017-09-24 03:22:32
@article{0f18013d-7546-4ee5-8d12-f625869a2471,
  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. (Blood. 2011;118(22):5905-5913)},
  author       = {Staffas, Anna and Kanduri, Meena and Hovland, Randi and Rosenquist, Richard and Ommen, Hans Beier and Abrahamsson, Jonas and Forestier, Erik and Jahnukainen, Kirsi and Jonsson, Olafur G. and Zeller, Bernward and Palle, Josefine and Lonnerholm, Gudmar and Hasle, Henrik and Palmqvist, Lars and Ehrencrona, Hans},
  issn         = {1528-0020},
  language     = {eng},
  number       = {22},
  pages        = {5905--5913},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia},
  url          = {http://dx.doi.org/10.1182/blood-2011-05-353185},
  volume       = {118},
  year         = {2011},
}