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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 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 Citation Map 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. Related Collections Neoplasia Oncogenes and Tumor Suppressors Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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 From the Laboratory of Allergic Diseases of the National Institute of Allergy and Infectious Diseases, the Cell and Cancer Biology Branch of the National Cancer Institute, and the the Autoimmunity Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, MD. 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 mesylate. The patient's bone marrow biopsy and aspirate displayed unique pathologic 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 mesylate 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 mesylate. (Blood. 2004;103:3222-3225) 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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PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects Blood, January 15, 2006; 107(2): 752 - 759. [Abstract] [Full Text] [PDF] M. M. Schittenhelm, S. Shiraga, A. Schroeder, A. S. Corbin, D. Griffith, F. Y. Lee, C. Bokemeyer, M. W.N. Deininger, B. J. Druker, and M. C. Heinrich Dasatinib (BMS-354825), a Dual SRC/ABL Kinase Inhibitor, Inhibits the Kinase Activity of Wild-Type, Juxtamembrane, and Activation Loop Mutant KIT Isoforms Associated with Human Malignancies Cancer Res., January 1, 2006; 66(1): 473 - 481. [Abstract] [Full Text] [PDF] J. Cammenga, S. Horn, U. Bergholz, G. Sommer, P. Besmer, W. Fiedler, and C. Stocking Extracellular KIT receptor mutants, commonly found in core binding factor AML, are constitutively active and respond to imatinib mesylate Blood, December 1, 2005; 106(12): 3958 - 3961. [Abstract] [Full Text] [PDF] H. 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