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 line into SCID (severe combined immunodeficient) mice and to examine anti-leukemic effects of fludarabine phosphate, a prodrug of 9-beta-D-arabinofuranosyl-2-fluoroadenine (2F-ara-A). In vitro cytotoxic screening pattern of 2F-ara-A differed from those of other anticancer agents. Intraperitoneal inoculation 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 hepatomegaly, splenomegaly and enlarged lymph nodes. The ascitic cells expressing the human B-lymphocytic cell surface antigen CD19 actually grew after a latent period of 15 days. In this model, twice daily administration of fludarabine 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 span of 32.9%, which was in a similar range to that of doxorubicin. Thus, intraperitoneal inoculation of the human JOK-1 CLL cells into SCID mice seems to serve as an animal model potentially for human leukemia, suggesting that transplantation and subsequent infiltration processes of human CLL cells is useful measures to explore mechanistic aspects for drug-induced modulation of the tumor progression.

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