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Blood, 15 April 2004, Vol. 103, No. 8, pp. 3222-3225. Prepublished online as a Blood First Edition Paper on December 24, 2003; DOI 10.1182/blood-2003-11-3816. This Article Full Text (PDF) All Versions of this Article: 2003-11-3816v1 103/8/3222    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Akin, C. Articles by Metcalfe, D. D Search for Related Content PubMed PubMed Citation Articles by Akin, C. Articles by Metcalfe, D. D Social Bookmarking                   What's this? Submitted November 7, 2003 Accepted December 13, 2003 A novel form of mastocytosis associated with a transmembrane c-Kit mutation and response to imatinib Cem Akin*, Gerard Fumo, Akif S Yavuz, Peter E Lipsky, Len Neckers, and Dean D Metcalfe National Institute of Allergy and Infectious Diseases, Laboratory of Allergic Diseases, National Institutes of Health, Bethesda, MD, USA National Cancer Institute, Cell and Cancer Biology Branch, National Institutes of Health, Bethesda, MD, USA National Institute of Arthritis and Musculoskeletal and Skin Diseases, Autoimmunity Branch, National Institutes of Health, Bethesda, MD, USA * Corresponding author; email: cakin{at}niaid.nih.gov. Mutational analysis of the c-kit gene in a patient with a previously undescribed variant of mast cell disease revealed a germline mutation, Phe522Cys, within the transmembrane portion of the Kit receptor protein. Transfection experiments revealed that the mutation caused ligand-independent autophosphorylation of Kit, which was inhibited by the tyrosine kinase inhibitor imatinib. The patient's bone marrow biopsy and aspirate displayed unique pathological features with the presence of excessive numbers of mature-appearing mast cells and absence of aberrant mast cell surface expression of CD2, CD25 and CD35. Therapy with imatinib resulted in a dramatic improvement in mast cell burden and clinical symptoms. These results highlight the significance of the transmembrane region of Kit in activation of the molecule and its importance in mast cell development, and suggest a role for screening for transmembrane c-kit mutations in patients with mastocytosis in association with the decision to use imatinib. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H.-P. 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