Abstract
Gene expression profiling has revealed molecular heterogeneity of diffuse large B cell lymphoma (DLBCL) in both humans and dogs. Two DLBCL subtypes based on cell of origin are generally recognized, germinal center B (GCB)-like and activated B cell (ABC)-like. A pilot study to characterize the transcriptomic phenotype of 11 dogs with multicentric BCL yielded two molecular subtypes distinguished on the basis of genes important in oxidative phosphorylation. We propose a metabolic classification of canine BCL that transcends cell of origin and shows parallels to a similar molecular phenotype in human DLBCL. We thus confirm the validity of this classification scheme across widely divergent mammalian taxa and add to the growing body of literature suggesting cellular and molecular similarities between human and canine non-Hodgkin lymphoma. Our data support a One Health approach to the study of DLBCL, including the advancement of novel therapies of relevance to both canine and human health.
Highlights
Diffuse large B cell lymphoma (DLBCL), an aggressive malignancy of mature B lymphocytes, comprises the most common subtype of non-Hodgkin lymphoma (NHL) [1]
Of the 11 selected genes, uchl1, s100a8, and s100a12 are of particular interest, all correlating with oxidative stress [13, 14]
Hierarchical clustering on the basis of the 22 human germinal center B (GCB)/activated B cell (ABC) classifier genes revealed distinct expression patterns of the two groups: genes highly expressed in GCB-diffuse large B cell lymphoma (DLBCL) were enriched in group 1, while genes highly expressed in ABC-DLBCL were enriched in group 2 (Figure 2C). These results suggested that the two dogs in group 1 were more likely to be of GCB phenotype, while the remaining nine dogs in group 2 were more likely to be of ABC phenotype, consistent with a skewed COO phenotypic distribution of the canine patients. This pilot study set out to characterize the transcriptomic signature of 11 dogs with DLBCL, aiming to refine the previously published canine DLBCL-subtyping COO classifier list
Summary
Diffuse large B cell lymphoma (DLBCL), an aggressive malignancy of mature B lymphocytes, comprises the most common subtype of non-Hodgkin lymphoma (NHL) [1]. Our previous study showed that overexpression of FoxP3 by intratumoral T cells in canine multicentric BCL correlates with shorter survival [8]. A gene profiling study has revealed GCB-like and ABC-like subtypes in canine DLBCL, the latter of which shows less favorable survival, resembling the human disease [9]. The same study proposed a list of 1,180 genes to distinguish GCB-DLBCL and ABC-DLBCL in dogs, prompting us to question whether a shorter list of selective classifiers may serve the same purpose. We undertook a pilot study to analyze the transcriptomic phenotype of dogs with multicentric BCL, all with the cytological characteristics of DLBCL, hypothesizing that molecular subtype may be identified by a selective subset of gene identifiers
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