Canine lymphoma as a comparative model for human non-Hodgkin lymphoma: recent progress and applications

Abstract

The term “lymphoma” describes a heterogeneous group of disorders involving monoclonal proliferation of malignant lymphocytes. As a group, lymphomas are among the most common tumors of dogs. Yet our enumeration and understanding of the many subtypes of lymphoma have been relatively slow, perhaps in part because for many years lymphoma was treated as a singular entity rather than a group of distinct diseases. The recognition that the full spectrum of lymphoid malignancies seen in humans also occurs in dogs, and that these tumors retain not only morphologic similarities and biological behavior but also synonymous driver molecular abnormalities, sets an ideal stage for dual-purpose research that can accelerate progress for these diseases in both species. Specifically, dogs represent exceptional models for defining causality, understanding progression, and developing new treatments for lymphoma in comparatively brief windows of time. Unique advantages of canine models include (1) spontaneous disease occurring without an isogenic background or genetic engineering; (2) chronology of disease adapted to lifespan, (3) shared environment and societal status that allows dogs to be treated as “patients,” while at the same time being able to ethically explore translational innovations that are not possible in human subjects; and (4) organization of dogs into breeds with relatively homogeneous genetic backgrounds and distinct predisposition for lymphomas. Here, we will review recent studies describing intrinsic and extrinsic factors that contribute to the pathogenesis of canine and human lymphomas, as well as newly developed tools that will enhance the fidelity of these models to improve diagnosis and develop new treatments.

In vitro drug sensitivity in canine lymphoma

“…These results correlate with a clinical investigation showing poorer prognosis in the case of high-grade T-cell canine lymphoma (6), and with the results of similar studies involving the use of established canine lymphoma and leukaemia cell lines (15). The use of drugs with proven in vitro activity against specific tumour cells may be useful in solving this problem.…”

First pathological study of canine primary breast lymphoma and the description of its clinicopathological characteristics as an animal model for human primary breast lymphoma

“…Extensive evidence suggests canine NHL to be a model for human NHL. Following the separation of canine lymphoma cells, the study by Ito et al (8) cultured and passaged them and developed a xenograft model. Subsequently, their molecular profile was examined and it was concluded that not only is canine NHL morphologically and behaviorally similar to human NHL, but its molecular changes also mimic human lymphoma.…”

“…As a result, invasion and metastasis can be followed in this model. Thirdly, with regard to the fact that dogs live alongside humans, they are exposed to the same risk factors and so the course of molecular changes and genetic mutations can also be studied (4,8,15).…”

A double blinded, placebo-controlled pilot study to examine reduction of CD34+/CD117+/CD133+ lymphoma progenitor cells and duration of remission induced by neoadjuvant valspodar in dogs with large B-cell lymphoma

“…These LPCs had phenotypic properties consistent with tumor-initiating or tumor-propagating cells (TIC/TPC); they also persisted in the xenotransplantation setting, suggesting that they were relevant to the biology of this disease in vivo 6 . When compared with the bulk of the tumor cells, LPCs showed significantly lower expression of 44 genes across the genome, mapping to cell cycle and transmembrane signaling pathways 7 . This indicated that LPCs exhibit the characteristic “slow proliferation” seen in normal bone marrow-derived hematopoietic stem cells and in TIC/TPC in other cancers.…”