Familial systemic mastocytosis with germline KIT K509I mutation is sensitive to treatment with imatinib, dasatinib and PKC412

Leuk Res. 2014 Oct;38(10):1245-51. doi: 10.1016/j.leukres.2014.07.010. Epub 2014 Aug 1.

Abstract

Mastocytosis are myeloproliferative neoplasms commonly related to gain-of-function mutations involving the tyrosine kinase domain of KIT. We herein report a case of familial systemic mastocytosis with the rare KIT K509I germ line mutation affecting two family members: mother and daughter. In vitro treatment with imatinib, dasatinib and PKC412 reduced cell viability of primary mast cells harboring KIT K509I mutation. However, imatinib was more effective in inducing apoptosis of neoplastic mast cells. Both patients with familial systemic mastocytosis had remarkable hematological and skin improvement after three months of imatinib treatment, suggesting that it may be an effective front line therapy for patients harboring KIT K509I mutation.

Keywords: Dasatinib; Familial mastocytosis; Imatinib; K509I KIT mutation; PKC412; Tyrosine kinase inhibitors.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / drug effects
  • Base Sequence
  • Benzamides / pharmacology
  • Blotting, Western
  • Dasatinib
  • Female
  • Germ-Line Mutation*
  • Humans
  • Imatinib Mesylate
  • Mastocytosis, Systemic / drug therapy*
  • Mastocytosis, Systemic / genetics*
  • Piperazines / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-kit / genetics*
  • Pyrimidines / pharmacology
  • Staurosporine / analogs & derivatives
  • Staurosporine / pharmacology
  • Thiazoles / pharmacology
  • Young Adult

Substances

  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Thiazoles
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit
  • Staurosporine
  • midostaurin
  • Dasatinib