Establishment of Bioluminescence Imaging Based Leukemia In Vivo Model for Preclinical Testing

Abstract 4879 Background. A hematological malignant animal model is an essential tool for evaluating efficacy of anti-cancer drugs and elucidating underlying mechanism of leukemogenesis. Intraperitoneal (IP) and intravenous (IV) xenograft of acute lymphoblastic leukemia (ALL) cells have limited capacity as in vivo anti-cancer drug screening system. Purpose. In this study, we aimed to establish an ALL animal model using NOD/SCID mouse and evaluate efficiency and sensitivity of the model as a preclinical drug screening system. Materials and Methods. Firefly luciferase (fLuc)-gene introduced ALL (ALL/fLuc) cell line and patient-originated ALL cells were transplanted into a tibia of NOD/SCID mouse. We conducted a comparative analysis of intra-bone marrow (IBMT) transplanted leukemia model with IP and IV transplantation of leukemic cells. Results. IBMT of ALL/fLuc cells effectively established a bioluminescent leukemia NOD/SCID mouse model. Upon comparison of IBMT model with IP and IV transplantation models, infusing identical number of ALL/fLuc cells into NOD/SCID mice resulted in IBMT model with evaluable bioluminescent signal, but not in IP and IV models. In IBMT model, bioluminescent signals of ALL/fLuc cells emitted from peripheral blood, tibia and infiltrated organs indicated that leukemia model was established. The changes in these signals9 strength reflected dose-dependent cytotoxic effects of vincristine, which allowed leukemia model with evaluable bioluminescent signal to be utilized as a preclinical drug screening system. IBMT leukemia model was also established using primary ALL cells that can provide additional insights for the development of leukemia therapeutics. Conclusion. IBMT of ALL/fLuc cells enables development of leukemia mouse model with the greater bioluminescent sensitivity than IP and IV in NOD/SCID to evaluate candidate for development of anti-cancer drug. Disclosures: No relevant conflicts of interest to declare.