Potential to target dysregulated interleukin-2 receptor expression in canine lymphoid and hematopoietic malignancies as a model for human cancer.

ABSTRACT

Lymphohematopoietic malignancies are common spontaneous diseases of dogs whose clinical presentation and biologic behavior closely resemble their human counterparts. The goal of this study was to define the potential to use canine lymphoma and leukemia as suitable models to refine therapeutic approaches targeting the interleukin-2 receptor (IL-2R). The authors evaluated the patterns of IL-2R expression in 13 dogs with multicentric non-Hodgkin's lymphoma (NHL) and in six dogs with leukemia (acute lymphocytic leukemia, n = 3; chronic lymphocytic leukemia in blast crisis, n = 1; acute monoblastic leukemia, n = 2). The authors first cloned and sequenced the complete coding domains of the wild-type canine IL-2R alpha-chain gene. They next used qualitative reverse transcription polymerase chain reaction (RT-PCR) analysis to examine IL-2R alpha, beta, and gamma(c) subunit expression in the tumors. Messenger RNA (mRNA) for the interleukin-2 receptor alpha, beta, and gammac subunits that comprise the high-affinity receptor was present in samples from all dogs with NHL. Expression of functional surface IL-2R also was observed flow cytometrically in NHL cells from all four dogs tested. Leukemic cells from one dog with B cell acute lymphocytic leukemia and two dogs with acute monoblastic leukemia expressed mRNA for all three subunits, whereas cells from another dog with B cell leukemia and both dogs with T cell leukemia expressed only mRNA for the beta and gammac subunits that comprise the intermediate-affinity receptor. These results indicate that the IL-2R is commonly expressed in canine lymphohematopoietic malignancies, and support the suitability of this large-animal model to evaluate targeted IL-2R cancer therapy using approaches of interest in the treatment of humans with hemolymphatic cancers.