RAS, FLT3, and C-KIT mutations in immunophenotyped canine leukemias.
OBJECTIVE
To determine the frequency of FLT3, C-KIT, and RAS mutations in canine leukemia patients.


METHODS
Ethylenediamine tetra-acetic acid blood samples were recruited from dogs with suspected leukemia, categorized by quantitative and cytological evaluation and immunophenotyping. Flow cytometry was carried out using antibodies against CD3; CD3e; CD4; CD5; CD8; CD11a, b, c, and d; CD14; CD21; CD34; CD45 and 45RA; CD79a; CD90 (THY-1); major histocompatibility complex II; myeloperoxidase; MAC387; and neutrophil-specific antibody. Genomic DNA was extracted from whole blood and analyzed for mutations in N, H, and K-RAS, FLT3, and C-KIT genes by polymerase chain reaction and sequencing.


RESULTS
Fifty-seven (77.0%) of 74 samples submitted from dogs with suspected leukemia had cytologically and immunophenotypically confirmed leukemia. There were 36 (63.2%) acute leukemias, 16 (28.1%) chronic, 3 (5.3%) prolymphocytic, 1 natural killer cell, and 1 chronic leukemia undergoing blast transformation. N-RAS mis-sense mutations were identified in 14 (25%) dogs with acute myeloid (AML) or lymphoid (ALL) leukemia, and also in one dog in the leukemic phase of lymphoma. Mutations in K-RAS were found in two dogs with AML. There were no H-RAS mutations. FLT3 internal tandem duplications were identified in three dogs with ALL, and a mis-sense mutation was found in one dog with ALL. C-KIT mutations were identified in three dogs with AML. Sixty-one percent of dogs with acute leukemia harbored mutations in N/K-RAS, FLT3, or C-KIT.


CONCLUSIONS
RAS, FLT3, and C-KIT mutations, analogous to those found in human leukemia, occur commonly in acute canine leukemia.
Usher
Suzanne G
SG
Small Animal Teaching Hospital, University of Liverpool, The Leahurst Campus, Neston, Wirral, UK.
Radford
Alan D
AD
Villiers
Elizabeth J
EJ
Blackwood
Laura
L
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism / Q000662:veterinary*; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics* / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
D015703:Antigens, CD; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3; D018631:ras Proteins