Abstract 4307: Characterization of a novel lymphoid progenitor population with predictive value in canine non-Hodgkin lymphoma

Abstract

Abstract Non-Hodgkin lymphoma (NHL) represents a heterogeneous group of lymphoid tumors divided into more than 25 subtypes. Histological classification and clinical stage are used to predict patient outcomes; however, disease progression is variable even within the same NHL subtype. Cancer stem cells (CSCs) are etiologically important cells that can maintain tumors, or whose frequency may reflect individual tumor biology. In terms of patient care and outcome, CSCs are considered to be resistant to conventional therapies. Thus, CSCs are not only etiologically important, but also might mediate treatment failure and relapse, suggesting they have prognostic impact for cancer. The presence and significance of CSCs or CSC-like progenitor cells in NHL has not been conclusively established. The objective of this study was to evaluate the existence and predictive value of lymphoid progenitor cells (LPCs) in dogs with naturally occurring NHL. We previously reported the use of flow cytometry to prospectively identify and enumerate cells in lymph nodes that co-expressed markers associated with hematopoietic progenitors (CD34, c-Kit, and CD133) and the common leukocyte antigen CD45. The number of these cells was inversely correlated (and predictive) for outcome following standard of care with CHOP-based chemotherapy. We now show that these cells represent an atypical lymphoid population, which harbors progenitor markers and lymphoid differentiation markers found within the B-cell phenotype (CD22+) comprising the malignant population. Furthermore, these cells appear to have clonal antigen receptor rearrangements that are related to the principal rearrangement found in the overall (progenitor antigen-negative) malignant cells. The number of progenitor marker- and CD22-positive cells was significantly greater (P=0.0017) in lymphoma samples as compared to lymph nodes from unaffected control dogs, where cells with this phenotype were present in vanishingly small numbers. Together, our results suggest that LPCs in malignant lymph nodes are not only predictive for survival of dogs with spontaneous NHL, but also may represent the CSC compartment for this disease (i.e., “lymphoma-initiating cells”). To confirm their CSC potential, we have adapted an in vitro culture system and a xenotransplantation model that will allow us to expand and serially transplant these primary canine B-cell lymphomas for more detailed studies. This project establishes a useful large animal (canine) model to test the validity of the cancer stem cell theory in non-Hodgkin lymphoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4307.