Barking up the right tree: advancing our understanding and treatment of lymphoma with a spontaneous canine model

Villarnovo, Dania; McCleary‐Wheeler, Angela L.; Richards, Kristy L.

doi:10.1097/moh.0000000000000357

Cited by 16 publications

(10 citation statements)

References 48 publications

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“…The value of the canine model has been the subject of several recent reviews (3,4) and generally lies in four areas: a preclinical model that has a shortened clinical course compared to human patients, fewer regulatory hurdles to experimental therapies and repeated sampling, the presence of a shared environment, and a degree of in-breeding which has created remarkable breed-specific patterns of disease for the discovery of genetic risk factors.…”

Section: Introductionmentioning

confidence: 99%

The Genetic and Molecular Basis for Canine Models of Human Leukemia and Lymphoma

Avery

2020

Front. Oncol.

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Emerging details of the gene expression and mutational features of canine lymphoma and leukemia demonstrate areas of similarities and differences between disease subsets in the humans and dogs. Many features of canine diffuse large B-cell lymphoma resemble the ABC form of human DLBCL, including constitutive activation of the NF-kB pathway, and almost universal presence of double expressing MYC/BCL2 lymphomas. Frequent TRAF3 mutations and absence of BCL6 expression are differences with the human disease that need further exploration. Canine peripheral T-cell lymphoma is more common in dogs than in people and behaves in a similarly aggressive manner. Common features of canine and human PTCL include activation of the PI3 kinase pathways, loss of PTEN, and the tumor suppressor CDKN2. There is insufficient data available yet to determine if canine PTCL exhibits the GATA3-TBX21 dichotomy seen in people. Common to all forms of canine lymphoproliferative disease are breed-specific predilections for subsets of disease. This is particularly striking in PTCL, with the Boxer breed being dramatically overrepresented. Breed-specific diseases provide an opportunity for uncovering genetic and environmental risk factors that can aid early diagnosis and prevention.

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Section: Introductionmentioning

confidence: 99%

The Genetic and Molecular Basis for Canine Models of Human Leukemia and Lymphoma

Avery

2020

Front. Oncol.

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“…Although a number of pivotal mechanistic studies on the pathobiology of cancer have been performed using the mouse as a model for humans, there is an unmet need for animal models that better recapitulate human cancer to investigate novel therapeutic targets, including cellular targets such as MDSCs 9,10 . Canine malignancies have already been recognized as strong comparative models for several human cancers 11,12 .…”

Section: Introductionmentioning

confidence: 99%

Phenotypic and transcriptomic characterization of canine myeloid-derived suppressor cells

Goulart

Hlavaty

Chang

et al. 2019

Sci Rep

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Myeloid-derived suppressor cells (MDSCs) are key players in immune evasion, tumor progression and metastasis. MDSCs accumulate under various pathological states and fall into two functionally and phenotypically distinct subsets that have been identified in humans and mice: polymorphonuclear (PMN)-MDSCs and monocytic (M)-MDSCs. As dogs are an excellent model for human tumor development and progression, we set out to identify PMN-MDSCs and M-MDSCs in clinical canine oncology patients. Canine hypodense MHC class II − CD5 − CD21 − CD11b + cells can be subdivided into polymorphonuclear (CADO48A + CD14 − ) and monocytic (CADO48A − CD14 + ) MDSC subsets. The transcriptomic signatures of PMN-MDSCs and M-MDSCs are distinct, and moreover reveal a statistically significant similarity between canine and previously published human PMN-MDSC gene expression patterns. As in humans, peripheral blood frequencies of canine PMN-MDSCs and M-MDSCs are significantly higher in dogs with cancer compared to healthy control dogs (PMN-MDSCs: p < 0.001; M-MDSCs: p < 0.01). By leveraging the power of evolution, we also identified additional conserved genes in PMN-MDSCs of multiple species that may play a role in MDSC function. Our findings therefore validate the dog as a model for studying MDSCs in the context of cancer.

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“…In recent years, naturally occurring canine tumours were regarded as potential models of human tumours. In particular, canine lymphoma shares many characteristics of human NHL, including clinical presentation, immunophenotypic composition, chemotherapeutic protocols, and response to treatment [20,21]. Therefore, canine lymphoma has been advocated as an ideal model for studying human NHL.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of miRNA and protein profiles within exosomes derived from canine lymphoid tumour cell lines

Asada

Tomiyasu

Uchikai³

et al. 2019

PLoS ONE

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Exosomes are small extracellular vesicles released from almost all cell types, which play roles in cell-cell communication. Recent studies have suggested that microenvironmental crosstalk mediated by exosomes is an important factor in the escape of tumour cells from the anti-tumour immune system in human haematopoietic malignancies. Here, we conducted comprehensive analysis of the miRNA and protein profiles within the exosomes released from four canine lymphoid tumour cell lines as a model of human lymphoid tumours. The results showed that the major miRNAs and proteins extracted from the exosomes were similar among the four cell lines. However, the miRNA profiles differed among the exosomes of each cell line, which corresponded to the expression patterns of the parent cells. In the comparison of the amounts of miRNAs and proteins among the cell lines, those of three miRNAs (miR-151, miR-8908a-3p, and miR-486) and CD82 protein differed between exosomes derived from vincristine-sensitive and resistant cell lines. Further investigations are needed to elucidate the biological functions of the exosomal contents in the microenvironmental crosstalk of lymphoid tumours.

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Barking up the right tree: advancing our understanding and treatment of lymphoma with a spontaneous canine model

Cited by 16 publications

References 48 publications

The Genetic and Molecular Basis for Canine Models of Human Leukemia and Lymphoma

The Genetic and Molecular Basis for Canine Models of Human Leukemia and Lymphoma

Phenotypic and transcriptomic characterization of canine myeloid-derived suppressor cells

Comprehensive analysis of miRNA and protein profiles within exosomes derived from canine lymphoid tumour cell lines

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