Acute myeloblastic leukemia with associated BCR‐ABL translocation in a dog

Abstract

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.

Comparative oncology: what dogs and other species can teach us about humans with cancer

“…RB1 deletions in chronic lymphocytic leukaemia and BCR-ABL fusion in chronic myeloid leukaemia (CML) were among the first cytogenetic aberrations detected in canine cancers that mirror the corresponding human cancers [107]. The BCR-ABL tyrosine kinase translocation (the so-called 'Raleigh chromosome' in dogs and 'Philadelphia chromosome' in humans) has since been demonstrated to be present in additional subtypes [108,109] and proven useful for monitoring cytogenetic remission in CMLs [110]. Another canine study included acute lymphoblastic leukaemia (ALL)/acute undifferentiated leukaemia (AUL) (N ¼ 11) and chronic lymphocytic leukaemia (CLL) (N ¼ 12) and demonstrated increased c-KIT expression in the ALL/AUL samples [111], offering the possibility of using tyrosine kinase inhibitors as a treatment option in canine leukaemia, an approach similar to that used for human leukaemia with tyrosine kinase-affected pathways.…”

Molecular characterization of canine BCR‐ABL–positive chronic myelomonocytic leukemia before and after chemotherapy

“…The BCR‐ABL fusion gene is evolutionarily conserved in canine chronic myeloid leukemia (CML). Termed the “Raleigh” chromosome, it has been identified using multicolor FISH, not only in several cases of canine CML, but also in one case of canine chronic monocytic leukemia (CMoL) and in one case of canine acute myeloid leukemia . In people, CML is a myeloproliferative disease characterized by uncontrolled proliferation of granulocytes and the presence of the Philadelphia chromosome.…”

Dysregulation of tyrosine kinases and use of imatinib in small animal practice

“…The BCR-ABL translocation has also been detected in three dogs with chronic monocytic leukaemia (Cruz Cardona et al, 2011;Culver et al, 2013;Pérez et al, 2013) and in one dog with acute myeloblastic leukaemia (Figueiredo et al, 2012) by FISH analysis. Although the nucleotide sequence of DNA fusion junctions for BCR-ABL translocations has not yet been analysed, these findings suggest the presence of BCR-ABL in a certain subset of leukaemia in dogs, which would make imatinib a potential therapeutic approach for these canine tumours, similar to humans.…”