A groundbreaking study has shed new light on the gene expression profile and cellular origins of canine peripheral T-cell lymphoma (PTCL), offering promising insights for both veterinary and human medicine. PTCL, a diverse group of T-cell cancers notorious for poor treatment responses, finds a parallel in the most common human subtype, PTCL-not otherwise specified (PTCL-NOS). This similarity has spurred interest in canine PTCL as a potential model for human PTCL research.

The study involved bulk RNA-sequencing of tumor samples from 33 dogs diagnosed with PTCL through flow cytometry. This comprehensive analysis included different PTCL types, such as CD4+, CD8+, and CD4-CD8- lymphomas. The team conducted extensive gene expression and clustering analyses, alongside gene set enrichment analysis to compare canine CD4+ PTCL with human PTCL-NOS, various oncogenic pathways, and stages of T-cell development.

Remarkably, the findings revealed that canine CD4+ PTCLs exhibited a consistent gene expression profile, mirroring the aggressive GATA3-PTCL subtype in humans. These cells showed increased GATA3 expression, upregulation of target genes, activation of the PI3K/AKT/mTOR signaling pathway, and decreased PTEN expression. In vitro assays further validated the dependency of these cells on the PI3K/AKT/mTOR pathway for survival and proliferation.

Furthermore, the study observed that canine CD4+ PTCL was enriched with thymic precursor gene signatures and displayed markers indicative of an immature cell state. This suggests that canine CD4+ PTCL might originate from an earlier stage of T-cell development compared to the traditionally assumed mature T-helper cell origin.

These findings not only enhance the understanding of canine PTCL but also hold significant implications for advancing the treatment and understanding of human PTCL-NOS. The study's comprehensive approach to deciphering the molecular underpinnings of this challenging disease marks a pivotal step forward in the ongoing battle against lymphoma.

Read full study here: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11762-w