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Background  The Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathways play important roles in the pathogenesis of diffuse large B cell lymphoma (DLBCL) in humans, and up‐regulated STAT3 expression and activity are associated with worse clinical outcome in humans. No studies have evaluated the JAK‐STAT signaling pathway in DLBCL of dogs.    Hypothesis  STAT3 pathway is deregulated in DLBCL in dogs. We aim to assess the expression, activation, and cellular localization of STAT3 and mitogen‐activated protein kinase ERK1/2 in DLBCL of dogs.    Animals  Forty‐three client‐owned dogs diagnosed with DLBCL by histopathology    Methods  Retrospective analysis of DLBCL in dogs, including patient characteristics and treatment, immunohistochemistry, and protein expressions by Western blot.    Results  A higher percentage of STAT3 and p‐STAT3 immunolabelled cells were observed in DLBCL of dogs when compared to normal canine lymph nodes. In STAT3 immunolabelled cells, STAT3 has higher nuclear expression in lymphoma samples than in normal or reactive lymph nodes. In addition to up‐regulated STAT3 expression and activation, mitogen‐activated kinase ERK1/2 activation is up‐regulated in DLBCL of dogs.    Conclusion and Clinical Importance  Compared with the normal canine lymph node, DLBCL of dogs has up‐regulated STAT3 pathway. Our results support future investigation of JAK inhibitors in the treatment of DLBCL in dogs.

STAT3 Expression and Activity are Up‐Regulated in Diffuse Large B Cell Lymphoma of Dogs