Research Study Update: Further Investigation of the Genes Controlling Canine Leukemia to Properly Diagnose and Control the Disease

AKC Canine Health Foundation Grant 1843
Principal Investigator: Dr. Matthew Breen, PhD; North Carolina State University

Entering second year of study, researchers comparing human and canine leukemia data

Leukemia represents a range of cancers, most often classified according to the type of blood cell affected and the clinical progression. Leukemia may be chronic, progressing slowly for many years with minimal symptoms, or acute, with sudden onset and rapid progression of symptoms, often resulting in euthanasia. The true incidence of leukemia in dogs is unknown, but consensus opinion is that many cases remain undiagnosed. In previous studies Dr. Breen found that canine leukemia presents with characteristic chromosomal and genetic changes shared with those known in human leukemia. In humans these chromosomal and genetic aberrations have been linked to disease progression and response to therapeutics, and in turn, this information drives clinical management of the patient.

In his current multicenter study Dr. Breen has obtained a large number of canine leukemia samples and assessed these by high resolution, genome-wide analysis of DNA copy number. One year into this two-year study they are ahead of schedule and have almost completed the molecular profiling of the cases proposed. They have identified regions of the canine genome that are subject to alterations in copy number more frequently in some subtypes of leukemia that others. Using sophisticated statistical analysis of the data they have begun to define a series of regions whose copy number status may be considered in combination to provide an accurate means to classify canine leukemia according to subtype. As they enter year two of this project they are armed with a substantial body of cytogenetic data from which to advance to the next phase of the study. They are now integrating the canine data with data from several hundred human cases, and have been able to identify numerous shared changes, many of which are associated with prognosis in human patients. As such, knowing that the underlying genomics is shared, they are moving toward developing a means to able to accurately diagnose canine leukemia and also to suggest possible treatments that may improve outcome, as in human patients. Many of the regions they have identified as copy number aberrant contain genes of interest to hematopoietic biology.  They may therefore add an aim to look more closely within these regions to compliment the general findings of Comparative Genomic Hybridization analysis and unravel some of the more complex underlying biology of leukemia.