Abstract
To promote cancer research and to develop innovative therapies, refined pre-clinical mouse tumor models that mimic the actual disease in humans are of dire need. A number of neoplasms along the B cell lineage are commonly initiated by a translocation recombining c-myc with the immunoglobulin heavy-chain gene locus. The translocation is modeled in the C.129S1-Ighatm1(Myc)Janz/J mouse which has been previously engineered to express c-myc under the control of the endogenous IgH promoter. This transgenic mouse exhibits B cell hyperplasia and develops diverse B cell tumors. We have isolated tumor cells from the spleen of a C.129S1-Ighatm1(Myc)Janz/J mouse that spontaneously developed a plasmablastic lymphoma-like disease. These cells were cultured, transduced to express eGFP and firefly luciferase, and gave rise to a highly aggressive, transplantable B cell lymphoma cell line, termed IM380. This model bears several advantages over other models as it is genetically induced and mimics the translocation that is detectable in a number of human B cell lymphomas. The growth of the tumor cells, their dissemination, and response to treatment within immunocompetent hosts can be imaged non-invasively in vivo due to their expression of firefly luciferase. IM380 cells are radioresistant in vivo and mice with established tumors can be allogeneically transplanted to analyze graft-versus-tumor effects of transplanted T cells. Allogeneic hematopoietic stem cell transplantation of tumor-bearing mice results in prolonged survival. These traits make the IM380 model very valuable for the study of B cell lymphoma pathophysiology and for the development of innovative cancer therapies.
Highlights
To assess the efficacy of novel anti-cancer therapies, refined preclinical mouse models that mimic the actual disease in humans need to be developed [1]
Translocations recombining C-MYC at 8q24 with the immunoglobulin heavy-chain gene locus, IGH, at 14q32 (8;14)(q24;q32) in B cells are seen as the initiating genomic event in Burkitt’s lymphoma [1,2,3,4,5] and this translocation is observed in other aggressive B cell tumors such as acute lymphoblastic leukemia [6,7] and plasmacytoma/multiple myeloma [8,9]
To characterize the immunophenotype of IM380 cells, we assessed the expression of a number of B cell markers and activation-associated surface proteins (Figure 1B)
Summary
To assess the efficacy of novel anti-cancer therapies, refined preclinical mouse models that mimic the actual disease in humans need to be developed [1]. More than two thirds of these mice develop mature B cell tumors between the age of 6 and 21 months resembling human endemic Burkitt’s lymphoma or plasmacytoma [10]. We have isolated tumor cells from the spleen of a C.129S1-Ighatm1(Myc)Janz/J mouse that spontaneously developed a plasmablastic lymphoma-like neoplasia.
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