Evaluation of tyrosine-kinase receptor c-KIT (c-KIT) mutations, mRNA and protein expression in canine leukemia : might c-KIT represent a therapeutic target?
Articolo
Data di Pubblicazione:
2013
Citazione:
Evaluation of tyrosine-kinase receptor c-KIT (c-KIT) mutations, mRNA and protein expression in canine leukemia : might c-KIT represent a therapeutic target? / M. Giantin, L. Aresu, A. Aricò, M.E. Gelain, F. Riondato, V. Martini, S. Comazzi, M. Dacasto. - In: VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY. - ISSN 0165-2427. - 152:3-4(2013 Apr), pp. 325-332. [10.1016/j.vetimm.2013.01.003]
Abstract:
The tyrosine-kinase receptor c-KIT (c-KIT) plays an important role in proliferation, survival
and differentiation of progenitor cells in normal hematopoietic cells. In human hematological
malignancies, c-KIT is mostly expressed by progenitor cell neoplasia and seldom by those
involving mature cells. Tyrosine kinase inhibitors (TKIs) are actually licensed for the firstand
second-line treatment of human hematologic disorders. Aim of the present study was
to evaluate c-KIT mRNA and protein expression and complementary DNA (cDNA) mutations
in canine leukemia. Eleven acute lymphoblastic leukemia (ALL) and acute undifferentiated
leukemia (AUL) and 12 chronic lymphocytic leukemia (CLL) were enrolled in this study.
The amounts of c-KIT mRNA and protein were determined, in peripheral blood samples, by
using quantitative real time RT-PCR, flow cytometry and immunocytochemistry, respectively.
The presence of mutations on c-KIT exons 8–11 and 17 were investigated by cDNA
sequencing. Higher amounts of c-KIT mRNA were found in ALL/AUL compared to CLL, and
this latter showed a lower pattern of gene expression. Transcriptional data were confirmed
at the protein level. No significant gain-of-function mutations were ever observed in both
ALL/AUL and CLL. Among canine hematological malignancies, ALL/AUL typically show a very
aggressive biological behavior, partly being attributable to the lack of efficacious therapeutic
options. The high level of c-KIT expression found in canine ALL/AUL might represent the
rationale for using TKIs in future clinical trials.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
c-KIT ; dog ; acute leukemia ; chronic lymphocytic leukemia ; tyrosine-kinase inhibitors
Elenco autori:
M. Giantin, L. Aresu, A. Aricò, M.E. Gelain, F. Riondato, V. Martini, S. Comazzi, M. Dacasto
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