Medium-sized FLT3 internal tandem duplications confer worse prognosis than short and long duplications in a non-elderly acute myeloid leukemia cohort

Magdalena Koszarska, Nora Meggyesi, Andras Bors, Arpad Batai, Otto Csacsovszki, Eniko Lehoczky, Emma Adam, Andras Kozma, Nora Lovas, Andrea Sipos, Tunde Krahling, Janos Dolgos, Peter Remenyi, Sandor Fekete, Tamas Masszi, Attila Tordai, Hajnalka Andrikovics

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4 Citations (Scopus)

Abstract

Internal tandem duplications (ITDs) of the fms-like tyrosine kinase 3 (FLT3) gene occur in about 25% of patients with adult acute myeloid leukemia (AML). The aim of our study was to investigate the frequency of FLT3-ITD mutations followed by a detailed analysis of the mutational load and size of ITD insertions in a cohort consisting of 324 patients younger than 60 years old and treated with curative intention. FLT3-ITD alone did not influence overall survival (OS) or disease-free survival (DFS). We observed worse OS and DFS for patients with high mutational load indicative for loss of the FLT3 wild type allele (p = 0.010, p = 0.038, respectively). In multivariate analyses, patients with FLT3-ITD48-60bp showed worse OS and DFS compared to other groups (FLT3-ITDneg, FLT3-ITD < 48b, FLT3-ITD> 60bp; p = 0.014, p = 0.019, respectively). Our novel observation suggested that not only high FLT3-ITD load, but also medium-sized ITD insertions (48-60 bp) represented an adverse prognostic subgroup of patients with AML.

Original languageEnglish
Pages (from-to)1510-1517
Number of pages8
JournalLeukemia and Lymphoma
Volume55
Issue number7
DOIs
Publication statusPublished - Jul 2014

Keywords

  • Acute myeloid leukemia
  • FLT3 internal tandem duplication
  • Molecular genetics
  • Mutation

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Koszarska, M., Meggyesi, N., Bors, A., Batai, A., Csacsovszki, O., Lehoczky, E., Adam, E., Kozma, A., Lovas, N., Sipos, A., Krahling, T., Dolgos, J., Remenyi, P., Fekete, S., Masszi, T., Tordai, A., & Andrikovics, H. (2014). Medium-sized FLT3 internal tandem duplications confer worse prognosis than short and long duplications in a non-elderly acute myeloid leukemia cohort. Leukemia and Lymphoma, 55(7), 1510-1517. https://doi.org/10.3109/10428194.2013.850163