ENGRAFTMENT OF CHRONIC PROLYMPHOCYTIC AND T-CELL LEUKEMIA IN SCID MICE

Engraftment of human acute leukemia cells in immunocompromised (SCID) mice has resulted in in vivo models for exploration of human tumor bio logy. Attempts at engraftment of chronic leukemia cells have been gene rally unsuccessful. We have engrafted cells from three human chronic l eukemias in SCID mice. Cell populations were from two patients with ch ronic lymphocytic leukemia (CLL) and either increased prolymphocytes ( CLL-Pro; patient 1), or prolymphocytic transformation (PLL; patient 2) and from a third patient with newly diagnosed T cell CLL. Both fresh and cryopreserved cells were used and were injected intravenously, int raperitoneally, or both, after conditioning with cyclophosphamide. In addition, cells derived from a mouse spleen engrafted with human leuke mia were passaged into another mouse. The animals were observed daily for signs of disease or appearance of tumors and sacrificed when termi nally ill. At intervals blood samples were obtained and analyzed for t he presence of human cells or DNA. Human leukemic cells were demonstra ted by polymerase chain reaction (PCR) analysis of the human DQ alpha gene or positive staining for human leukocyte common antigen (LCA). Th e presence of Epstein-Barr virus (EBV)-positive cells was also investi gated by PCR analysis. Disseminated tumors developed in most mice inoc ulated with cells from the first patient, and this was associated with shortened survival times. The method of administration, use of fresh or frozen samples, or the size of the inoculum had no effect on the de velopment of leukemia. Survival of the mouse receiving passaged cells was similar to mice inoculated with fresh cells. Extensive histologic, immunophenotypic, and DNA studies were performed on organs from mice engrafting with cells from patient 1. PCR analysis for EBV sequences w as negative in the mice engrafting from all three cases. The successfu l engraftment of human CLL-Pro PLL and T cell CLL in SCID mice, and th e reproducibility of this effect using frozen cells, will provide a mo del for exploration of disease biology and for investigations of new d rugs or combinations that may be useful in the treatment of CLL.