Development of intermediate-grade (mantle cell) and low-grade (small lymphocytic and marginal zone) human non-Hodgkin's lymphomas xenotransplanted insevere combined immunodeficiency mouse models

We have used severe combined immunodeficiency (SCID) (c.b.-17, ICR/SCID) mi ce to develop xenotransplantation (XT) models for human intermediate-and-lo w-grade non-Hodgkin's lymphomas (NHL). In the past, SCID mice have provided a variety of useful XT models for human hematopoietic neoplasms that prima rily involve the acute leukemias and some nonhematopoietic tumors, but only rare reports exist on use of the SCID mouse model in the study of primary tumor cells from NHL intermediate-grade and low-grade NHL are the most comm on lymphomas seen in adults. There is no effective therapy for those types of NHL, and they have not been established in an animal model to date. The lack of an animal model has hampered studies that can evaluate the disease process in vivo as well as the definition of therapeutic parameters involve d in treatment. We report in this study that primary patient samples of NHL (intermediate grade and low grade) have been successfully established in S CID mice after XT. NHL include intermediate-grade (mantle cell lymphoma) an d low-grade (eg, small lymphocytic lymphoma/chronic lymphocytic lymphoma an d marginal zone lymphoma) forms. Studies have been directed toward creating appropriate conditions for the optimal grafting of these NHL in SCID mice so that the disease process in humans could be accurately simulated. These studies indicate that development of XT-human lymphoma cells in SCID mice a ppear to be linked to their biologic and/or clinical behavior, transplanted lymphoma cell number, and age, as well as to the natural killer cell statu s of the SCID mouse recipients. Evidence has also shown that NHL cells can exhibit homing or trafficking patterns in SCID recipients that resemble tho se observed in patients with gastrointestinal lymphomatous involvement (par ticularly that of mantle cell lymphoma). Our studies also indicate that art efactual influences, such as the outgrowth of Epstein-Barr virus-associated lymphoblastoid lesions, are rare occurrences in the human NHL/SCID models that we have established.