A human B-cell CLL model established by transplantation of JOK-1 cells into SCID mice and an anti-leukemia efficacy of fludarabine phosphate

The present study was carried out to establish a human chronic lymphocytic leukemia (CLL) mouse model by transplantation of a JOK-1 human CLL cell lin e into SCID (severe combined immunodeficient) mice and to examine anti-leuk emic effects of fludarabine phosphate, a prodrug of 9-beta-D-arabinofuranos yl-2-fluoroadenine (2F-ara-A). In Vitro cytotoxic screening pattern of 2F-a ra-A differed from those of other anticancer agents. Intraperitoneal inocul ation with JOK-1 cells in SCID mice allowed the cells to infiltrate into a variety of organs including the liver and thymus, and resulted in the death of the mice with a median survival time of 29.5 days, associated with hepa tomegaly, splenomegaly and enlarged lymph nodes. The ascitic cells expressi ng the human B-lymphocytic cell surface antigen CD19 actually grew after a latent period of 15 days. In this model, twice daily administration of flud arabine phosphate at a dose of 135 mg/kg for 5 days prolonged the survival time of the mice for considerably longer period than once-a-day treatment. Fludarabine phosphate in the doubled course of twice daily increased life s pan of 32.9%, which was in a similar range to that of doxorubicin. Thus, in traperitoneal inoculation of the human JOK-1 CLL cells into SCID mice seems to serve as an animal model potentially for human leukemia, suggesting tha t transplantation and subsequent infiltration processes of human CLL cells is useful measures to explore mechanistic aspects for drug-induced modulati on of the tumor progression.