ESTABLISHMENT OF A HUMAN B-CLL XENOGRAFT MODEL - UTILITY AS A PRECLINICAL THERAPEUTIC MODEL

Chronic lymphocytic leukemia (CLL), a proliferative disease of mature looking B lymphocytes, is the commonest leukemia in western countries. It remains incurable by available treatment modalities. We report on the establishment of a permanent, EBV-negative, B-CLL line (WSU-CLL) f rom the peripheral blood of a patient with CLL. The cells grow as susp ension in liquid culture, express IgG lambda and other B cell markers and show Ig heavy and light gene rearrangements. Karyotypic analysis s hows 45,X,del(3)(p14;p24),t(4;12;12) (q31;q22;p13), t(5;12) (q31;p13), add(16)(q24)X2, t(18;21) (q12;p12). WSU-CLL forms colonies when grown on soft agar. A xenograft model was established by injecting the WSU- CLL cells subcutaneously (s.c.) in severe combined immune deficient (S CID) mice. When the s.c. tumor was transplanted in vivo to other SCID mice, the success rate was 100% with a doubling time of 7.3 days. The CLL-SCID xenograft model was used to test the efficacy of selected sta ndard chemotherapy drugs and new therapeutic agents against WSU-CLL. T he cell line and the xenograft described can be used as a model to fac ilitate the development of new therapeutic agents against CLL in man.