Lymphoid progenitor cells linked to outcome in dog B-cell lymphoma

Abstract

Abstract Disease progression and response to treatment in people and in pet dogs with non-Hodgkin B-cell lymphoma (NHL) can be unpredictable, even for patients with the same subtype of disease, reflecting the heterogeneous nature of these tumors. Tumor angiogenesis has been correlated with stage and progression of lymphoid tumors in humans and in dogs, but the prognostic value of mature endothelial cells (ECs) and endothelial progenitor cells (EPCs) as surrogate markers for angiogenesis in NHL is unclear. Furthermore, the significance of lymphoid progenitor cells (LPCs) in this disease has not been addressed. Here, we evaluated the predictive value of ECs, EPCs and LPCs in dogs with naturally occurring NHL. We used flow cytometry to identify prospectively cells that co-expressed CD34, c-Kit, and/or CD133 with αvβ3-integrin (EPCs); or with CD45 and lymphoid lineage markers (LPCs), as well as cells that expressed CD146 (ECs), in blood and lymph nodes from dogs with NHL treated using standard of care multi-agent chemotherapy. The normalized frequency of ECs, EPCs and LPCs was compared with patient outcomes. ECs, EPCs, and LPCs were routinely present in all lymph node samples. No correlation was observed between ECs and EPCs and patient outcomes; conversely, there was a significant (p<0.05) inverse correlation between LPCs and overall survival. Our results suggest that a population of cells with lymphoid progenitor phenotypes is predictive for survival outcomes in spontaneous canine NHL.