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Leuk Lymphoma. 2014 Jul;55(7):1510-7. doi: 10.3109/10428194.2013.850163. Epub 2013 Nov 25.

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

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Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service , Budapest , Hungary.


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.


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

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