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A novel FLT3 activation loop mutation N841K in acute myeloblastic leukemia

Leukemia volume 19, pages 480–481 (2005)Cite this article

TO THE EDITOR

Fms-like tyrosine kinase 3 (FLT3) is a member of the class III receptor tyrosine kinase subfamily and plays an important role in the proliferation of hematopoietic progenitors. The internal tandem duplications (ITDs) in the juxtamembrane (JM) domain of FLT3 are demonstrated in approximately 20% of acute myeloblastic leukemia (AML) patients. FLT3-ITDs are associated with increased leukocyte counts and are more prevalent in AML patients with normal karyotype. Furthermore, FLT3-ITDs are associated with high relapse rate in patients with AML. In addition, substitution mutations in the second tyrosine kinase (TK2) domain at D835 of the FLT3 gene have recently been reported in approximately 7% of patients with AML.1,2 Both the FLT3-ITD and FLT3-D835 mutations result in constitutive activation of the receptor that probably confers a proliferative benefit to AML cells with ligand-independent dimerization, autophosphorylation and activation of downstream pathways. As FLT3 mutations have been implicated in the pathogenesis of AML and are potential therapeutic targets for specific tyrosine kinase inhibitors, a complete characterization of FLT3 mutations would be necessary.

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Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Science and Culture, and Public Trust Haraguchi Memorial Cancer Research Fund.

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  1. Department of Internal Medicine II, Kumamoto University School of Medicine, Kumamoto, Japan

    N Matsuno, T Nanri, T Kawakita, H Mitsuya & N Asou

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  1. N Matsuno
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  2. T Nanri
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  3. T Kawakita
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  4. H Mitsuya
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Correspondence to N Asou.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu).

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Matsuno, N., Nanri, T., Kawakita, T. et al. A novel FLT3 activation loop mutation N841K in acute myeloblastic leukemia. Leukemia 19, 480–481 (2005). https://doi.org/10.1038/sj.leu.2403630

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