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

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-ITD^48–60bp showed worse OS and DFS compared to other groups (FLT3-ITD^neg, 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.

Keywords::

• Acute myeloid leukemia
• FLT3 internal tandem duplication
• mutation
• molecular genetics

Acknowledgements

The authors wish to thank the late Sarolta Nahajevszky for initiating and coordinating clinical data acquisition and analysis of patients with AML in her lifetime. We would like to thank Horváth Csongorné, Pfundt Antalné, Csehné Bánhidi Klára and Petró Péterné for their technical assistance.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This work was supported by grants from OTKA (K104903), and COST Action BM0801. H.A. is a recipient of the Janos Bolyai Research Scholarship from the Hungarian Academy of Sciences.