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Clinical Laboratory Correlates: AML And Flt3 Gene

Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene

Leukemia volume 14, pages 675–683 (2000)Cite this article

Abstract

Internal tandem duplications of the Flt3 gene (Flt3/ITDs) are present in about 18% of all AML cases and are therefore one of the most frequent somatic gene mutations in AML. Little is known about the role of Flt3/ITDs in leukemogenesis or their clinical relevance. In this study we compared 18 samples with Flt3/ITDs and 63 AML samples without these mutations with respect to clinical prognosis, cytokine responsiveness, progenitor cell content and repopulation in the NOD/SCID mouse. We found that in patients with a mutation CR rates are reduced (P = 0.03) and relapse rates are increased (P = 0.01), indicating the prognostic importance of Flt3/ITDs. This is also emphasized by the finding that in patients under the age of 60 years, as well as in older patients the event-free survival was more unfavorable for the mutant patients (P = 0.003 and P = 0.03, respectively). At diagnosis Flt3/ITD and non-mutant AML bone marrow samples did not differ in their progenitor/stem cell frequencies. Cobblestone area forming cell (CAFC) subsets showed a similar frequency distribution in mutant and non-mutant samples. In 7-day liquid cultures, Flt3/ITD samples showed a reduced growth in response to a variety of myeloid growth factors. In contrast, Flt3/ITD samples displayed a higher ability to engraft the NOD/SCID bone marrow with leukemic cells. Together these data show that the Flt3/ITD represents an important diagnostic marker for patient prognosis, and that the presence of these mutations is associated with altered proliferative ability of progenitors in vivo and in vitro.

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Acknowledgements

This project is financed by the Dutch platform for alternatives in animal research (PAD) grant No. VWS/PAD 9625.

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Authors and Affiliations

  1. Dept of Haematology, Erasmus University, Rotterdam, The Netherlands

    WJC Rombouts, I Blokland, B Löwenberg & RE Ploemacher

  2. Dept of Haematology, Dijkzigt University Hospital, Rotterdam, The Netherlands

    B Löwenberg

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Rombouts, W., Blokland, I., Löwenberg, B. et al. Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene. Leukemia 14, 675–683 (2000). https://doi.org/10.1038/sj.leu.2401731

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