RESUMEN
Treatment of chronic monocytic leukemia (CMoL) in dogs has traditionally consisted of hydroxyurea. The use of tyrosine kinase inhibitors has been proposed as a treatment option for dogs with CMoL but has never been reported. We report a case of CMoL in a young dog that achieved clinical remission with treatment with the tyrosine kinase inhibitor toceranib and prednisone.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Proteínas de Fusión bcr-abl/genética , Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/veterinaria , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Proliferación Celular/efectos de los fármacos , Enfermedades de los Perros/genética , Perros , Femenino , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Hibridación Fluorescente in Situ , Indoles/administración & dosificación , Indoles/uso terapéutico , Leucemia Mieloide/genética , Leucemia Mieloide/patología , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Pirroles/administración & dosificación , Pirroles/uso terapéutico , Translocación Genética , Resultado del TratamientoRESUMEN
Genetic aberrations linked to tumorigenesis have been identified in both canine and human hematopoietic malignancies. While the response of human patients to cancer treatments is often evaluated using cytogenetic techniques, this approach has not been used for dogs with comparable neoplasias. The aim of this study was to demonstrate the applicability of cytogenetic techniques to evaluate the cytogenetic response of canine leukemia to chemotherapy. Cytology and flow cytometric techniques were used to diagnose chronic myelomonocytic leukemia in a dog. High-resolution oligonucleotide array comparative genomic hybridization (oaCGH) and multicolor fluorescence in situ hybridization (FISH) were performed to identify and characterize DNA copy number aberrations (CNAs) and targeted structural chromosome aberrations in peripheral blood WBC at the time of diagnosis and following one week of chemotherapy. At the time of diagnosis, oaCGH indicated the presence of 22 distinct CNAs, of which trisomy of dog chromosome 7 (CFA 7) was the most evident. FISH analysis revealed that this CNA was present in 42% of leukemic cells; in addition, a breakpoint cluster region-Abelson murine leukemia viral oncogene homolog (BCR-ABL) translocation was evident in 17.3% of cells. After one week of treatment, the percentage of cells affected by trisomy of CFA7 and BCR-ABL translocation was reduced to 2% and 3.3%, respectively. Chromosome aberrations in canine leukemic cells may be monitored by molecular cytogenetic techniques to demonstrate cytogenetic remission following treatment. Further understanding of the genetic aberrations involved in canine leukemia may be crucial to improve treatment protocols.
Asunto(s)
Cromosomas Humanos Par 7/genética , Enfermedades de los Perros/genética , Proteínas de Fusión bcr-abl/genética , Leucemia Mielomonocítica Crónica/veterinaria , Trisomía/genética , Animales , Hibridación Genómica Comparativa/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/patología , Perros , Humanos , Hibridación Fluorescente in Situ/veterinaria , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Leucemia Mielomonocítica Crónica/genética , Leucemia Mielomonocítica Crónica/patología , MasculinoRESUMEN
An 8-year-old male neutered Labrador Retriever was referred to the University of Wisconsin Veterinary Medical Teaching Hospital with a presumptive diagnosis of leukemia. Hematologic abnormalities included normal neutrophil count with a left shift, monocytosis, eosinophilia, thrombocytopenia, and circulating immature mononuclear cells. Bone marrow was effaced by immature hematopoietic cells of various morphologic appearances. In addition, large multinucleated cells were observed frequently. Flow cytometric analysis of nucleated cells in blood revealed 34% CD34(+) cells, consistent with acute leukemia. By immunocytochemical analysis of cells in blood and bone marrow, some mononuclear cells expressed CD18, myeloperoxidase, and CD11b, indicating myeloid origin; some, but not all, large multinucleated cells expressed CD117 and CD42b, the latter supporting megakaryocytic lineage. The diagnosis was acute myeloblastic leukemia without maturation (AML-M1). To identify genetic aberrations associated with this malignancy, cells from formalin-fixed paraffin-embedded bone marrow were analyzed cytogenetically by multicolor fluorescence in situ hybridization (FISH). Co-localization of bacterial artificial chromosome (BAC) containing BCR and ABL was evident in 32% of cells. This confirmed the presence of the canine BCR-ABL translocation or Raleigh chromosome. In people, the analogous translocation or Philadelphia chromosome is characteristic of chronic myelogenous leukemia (CML) and is rarely reported in AML. BCR-ABL translocation also has been identified in dogs with CML; however, to our knowledge this is the first report of AML with a BCR-ABL translocation in a domestic animal.