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Spotlight on Acute Promyelocytic Leukemia

Alterations of the FLT3 gene in acute promyelocytic leukemia: association with diagnostic characteristics and analysis of clinical outcome in patients treated with the Italian AIDA protocol

Leukemia volume 16, pages 2185–2189 (2002)Cite this article

Abstract

Alterations in the FLT3 gene, including internal tandem duplications (ITDs) and D835 mutations occur frequently in acute myelogenous leukemia. We investigated the prevalence and clinico-biological correlations of FLT3 ITDs and D835 mutations in 90 patients with acute promyelocytic leukemia (APL) receiving the AIDA protocol. Twenty patients in which both presentation and relapse material was available were analyzed sequentially. Thirty-three patients (37%) harbored the ITD, and seven (7.7%) the D835 mutation in blasts obtained at diagnosis. Presence of ITDs was strongly associated with high WBC count (P = 0.0001), M3 variant (P = 0.0004), and the short (BCR3) PML/RARα isoform (P = 0.003). There was no difference in response to induction in the two ITD+ve and ITD−ve groups, while a trend towards inferior outcome was observed for ITD+ve cases when analyzing disease-free survival (DFS) and relapse risk (RR). These differences, however, did not reach statistical significance. Sequential studies showed variable patterns in diagnostic and relapse material, ie ITD (−ve/−ve, +ve/+ve, +ve/−ve, −ve/+ve) and D835 (−ve/−ve, +ve/−ve, −ve/+ve). Our results indicate that FLT3 alterations are associated in APL with more aggressive clinical features and suggest that these lesions may not play a major role in leukemia progression.

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Acknowledgements

This study was supported by grants from AIL, AIRC, MURST and Ministero della Salute. At the time of this study, NIN was on leave of absence from Dept of Chemical Biochemistry (Hematology) Universidad Nacional de Rosario (Argentina), while VC was on leave from the Dept of Hematology, Republic University, Army Hospital and AEPSM, Montevideo, Uruguay. We are indebted to Dr Guillermo Martin for helpful comments and statistical analysis.

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  1. Department of Cellular Biotechnologies and Hematology, University La Sapienza of Roma, Italy

    NI Noguera, M Breccia, M Divona, D Diverio, V Costa, S De Santis, G Avvisati, MB Pinazzi, MC Petti, F Mandelli & F Lo Coco

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Noguera, N., Breccia, M., Divona, M. et al. Alterations of the FLT3 gene in acute promyelocytic leukemia: association with diagnostic characteristics and analysis of clinical outcome in patients treated with the Italian AIDA protocol. Leukemia 16, 2185–2189 (2002). https://doi.org/10.1038/sj.leu.2402723

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