RAS, FLT3, and C-KIT mutations in immunophenotyped canine leukemias
| Autor: | Alan D Radford, Suzanne G. Usher, Elizabeth J. Villiers, Laura Blackwood |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Canine Leukemia
Cancer Research Pathology medicine.medical_specialty Myeloid Biology medicine.disease_cause Immunophenotyping Dogs Antigens CD hemic and lymphatic diseases Genetics medicine Animals Dog Diseases Molecular Biology Mutation Acute leukemia Leukemia Cell Biology Hematology medicine.disease Molecular biology Proto-Oncogene Proteins c-kit medicine.anatomical_structure Chronic leukemia fms-Like Tyrosine Kinase 3 Acute Disease Chronic Disease ras Proteins CD5 |
| Zdroj: | Experimental hematology. 37(1) |
| ISSN: | 1873-2399 |
| Popis: | Objective To determine the frequency of FLT3, C-KIT, and RAS mutations in canine leukemia patients. Materials and 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. Conclusion RAS, FLT3, and C-KIT mutations, analogous to those found in human leukemia, occur commonly in acute canine leukemia. |
| Databáze: | OpenAIRE |
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