A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib

Blood. 2004 Apr 15;103(8):3222-5. doi: 10.1182/blood-2003-11-3816. Epub 2003 Dec 24.


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.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amino Acid Substitution
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Bone Marrow / pathology
  • Female
  • Germ-Line Mutation*
  • Humans
  • Imatinib Mesylate
  • In Vitro Techniques
  • Mast Cells / drug effects
  • Mast Cells / pathology
  • Mastocytosis, Systemic / drug therapy*
  • Mastocytosis, Systemic / genetics*
  • Mastocytosis, Systemic / pathology
  • Piperazines / therapeutic use*
  • Proto-Oncogene Proteins c-kit / genetics*
  • Pyrimidines / therapeutic use*


  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit