Evaluation of c-KIT (CD117) mutations, mRNA and protein expression in canine leukemia and lymphoma: might c-KIT represent a therapeutical target?

Introduction: In normal hematopoietic cells, c-KIT plays an important role in proliferation, survival and differentiation of progenitor cells. Upon maturation, its expression is lost except in mast cells, natural killer and dendritic cells. In human hematopoietic malignancies, c-KIT is mostly expressed by progenitor cell neoplasms and seldom by those involving mature cells. Aim of this study was to evaluate c-KIT expression in canine hematopoietic malignancies, as there are currently no data reported in the veterinary literature. Materials and Methods: Sixty-nine canine lymphoid neoplasms, including 25 B-cell lymphomas (B), 21 T-cell lymphomas (T), 11 acute lymphoid leukemias (ALL) and 12 chronic lymphocytic leukemias (CLL) were enrolled. c-KIT expression (mRNA and protein) in lymph node fine needle aspirates and peripheral blood was measured by using quantitative Real Time RT-PCR, flow cytometry and immunocytochemistry. Mutations on c-KIT exons 8, 9, 10, 11 and 17 were investigated by means of complementary DNA sequencing. Results: High amounts of c-kit mRNA were noticed in ALL, whereas CLL, B and T-lymphoma showed a comparatively lower gene expression. Transcriptional data were confirmed at the protein level; moreover, c-KIT localization was shown to be mostly membranous. No significant gain-of-function mutations were observed. Conclusions: Among canine haematological malignancies, ALL typically shows a very aggressive biological behavior, partly being attributable to the lack of efficacious treatment options. The expression of c-KIT in canine ALL, as evidenced by this study, may represent the rationale for using tyrosine kinase inhibitors in future clinical trials.