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Keywords:

  • mastocytosis;
  • cancer;
  • cell toxicity;
  • gene therapy

Summary

Gain-of-function mutations of kit tyrosine kinase receptor are associated with mastocytosis. Two subclones of the HMC1 mast leukaemia cell line were used; both express an identical KIT allele-specific regulatory type mutation (V560G), but differ in that one also expresses an enzymatic site type mutation (D816V) that confers on them resistance to imatinib mesylate tyrosine kinase inhibitor. In both cell lines, proliferation was suppressed and apoptosis induced by the combination of KIT gene silencing and α-tocopherol succinate (α-TOS), a derivate of α-tocopherol, also known as vitamin E. Furthermore, HMC1 cells with decreased kit levels by KIT silencing, failed to form tumours when xenotransplanted into immunocompromised mice and the animals were treated systemically with α-TOS. Targeting kit in the presence of α-TOS represents a new approach against proliferation of human mast leukaemia cell lines.