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The size of duplication does not add to the prognostic significance of FLT3 internal tandem duplication in acute myeloid leukemia patients

Leukemia volume 20, pages 2074–2076 (2006)Cite this article

The fms-like tyrosine kinase 3-FLT3 gene encodes a class 3 receptor tyrosine kinase for the FLT3 ligand, that is normally expressed in CD34+ hematopoietic stem/progenitor cells and plays a fundamental role in both normal and leukemic hematopoiesis.1 Tandem internal duplication of the FLT3 gene (FLT3/ITDs) represents one of the most common molecular abnormalities in patients with acute myeloid leukemia (AML), and can be detected in around 25% of all patients.2 This abnormality consists of in-frame insertions of duplicated sequences localized in the juxtamembrane region of the molecule, and results in the constitutive, ligand independent, activation of the tyrosine kynase activity of the FLT3 receptor; this in turn would be responsible for the abnormal proliferation and differentiation of FLT3 mutated leukemia stem cells.1 From a clinical point of view, the presence of FLT3/ITDs confers a worse prognosis due to an increased relapse rate, adverse disease-free survival (DFS) and reduced overall survival (OS), while the rate of complete remission (CR) is not significantly affected.3, 4 The effects on OS are independent of the cytogenetic risk category.3 The molecular characteristics of FLT3/ITDs are extremely variable among patients because of the different mutated to wild-type (WT) allele ratios and the wide size of duplicated sequences, that range from a few to hundreds of nucleotides (nt). It has been shown that patients with the highest FLT3/ITDs/FLT3WT ratios, and even more hemizygous FLT3/ITDs patients who lack normal FLT3,5 present a particularly adverse disease outcome.3, 5 Furthermore, Stirewalt et al.6 recently reported that the presence of longer ITDs associated with decreasing OS and RFS, suggesting that FLT3/ITD size may have prognostic significance.

The aim of this study was to evaluate whether determining the size of the FLT3 internal tandem duplication would add to prognosis assessment in a population of adult AML patients diagnosed and treated in our Institution.

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Authors and Affiliations

  1. Department of Hematology, University of Florence, Florence, Italy

    V Ponziani, G Gianfaldoni, F Mannelli, F Leoni, S Ciolli, P Guglielmelli, E Antonioli, G Longo, A Bosi & A M Vannucchi

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  1. V Ponziani
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  2. G Gianfaldoni
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Correspondence to A M Vannucchi.

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Ponziani, V., Gianfaldoni, G., Mannelli, F. et al. The size of duplication does not add to the prognostic significance of FLT3 internal tandem duplication in acute myeloid leukemia patients. Leukemia 20, 2074–2076 (2006). https://doi.org/10.1038/sj.leu.2404368

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