An Animal Model for Anaplastic Large Cell Lymphoma in the Immunocompetent Syngeneic C57Bl/6 Mouse

Abstract

SUMMARY:We report on the analysis of a murine anaplastic lymphoid cell line TS1G6, established recently by interleukin (IL)-9 transfection. TS1G6 revealed a highly characteristic pattern of large anaplastic cells with mononuclear, binuclear, or multinuclear cells resembling Hodgkin (H) or Sternberg-Reed (SR) cells. This cell line is tumorigenous after injection of as few as 10 4 lymphoma cells into nude or immunocompetent C57Bl/6 mice and leads to death from progressive disease of all treated animals within a few weeks. The histological analysis of these tumors revealed a diffuse large cell malignant lymphoma that is morphologically almost identical to human anaplastic large cell lymphoma (ALCL). The lymphoma cells did not show overexpression of the anaplastic lymphoma kinase (ALK) gene, which is found in about 50% of the cases of human ALCL. Thus, this model may be an animal model for an important subset of human ALCL. The cytokine profile, which is of the T helper 2 type, showed strong parallels to the human lymphoma counterpart. Mice suffering from such lymphomas could not be cured with a regimen using high dose cyclophosphamide similar to many ALCL patients. Such an animal model for ALCL has not yet been recognized, but may provide the basis for investigating new antitumor immunotherapies in a fully immunocompetent host . (Lab Invest 2000, 80:1523-1531.

Cytogenetic characteristics of a murine in vitro model for the human anaplastic large cell lymphoma (ALCL)

“…No alteration of chromosome 17 was detectable by SKY, confi rming the results of Bittner et al (2000). However, dicentric as well as isodicentric chromosomes were detected.…”

“…The investigated cell line TS1G6 was established by (IL)-9 transfection and is tumorigenic after injection into immunocompetent mice. The cell line, morphologically and immunohistochemically characterized by Bittner et al (2000), shows similarities to the human ALK-negative ALCL. SKY analysis showed a hypotetraploid chromosome complement with complex structural aberrations.…”

“…TS1G6 cells are positive for CD3, CD4, CD25, CD30, and CD71, thus resembling the typical immunophenotype of ALCL. They do not express ALK, and thus represent an ALK-negative subtype of the human ALCL (Bittner et al, 2000). Here, we aimed to characterize the murine anaplastic lymphoid cell line TS1G6 using spectral karyotyping (SKY) and single-color fl uorescence in situ hybridization (FISH).…”

Interleukin-9 (IL-9) and NPM-ALK each generate mast cell hyperplasia as single ‘hit’ and cooperate in producing a mastocytosis-like disease in mice

“…Affected mouse tissues were characterized immunophenotypically using the ABC-technique [59]. A panel of biotinylated first-step antibodies (all purchased from BD Bioscience, Heidelberg, Germany) was used: B-cell markers included CD45R, CD19, CD38 and CD23, and T-cell markers included CD5, CD25, CD4, CD8 and CD3e.…”

“…In malignant lymphomas carrying the t(2;5)(p23;q35), ALK is usually fused to the nucleophosmin (NPM) gene [54][55][56]. We and others have shown that NPM-ALK leads to the formation of malignant lymphomas in mice [57][58][59][60]. In addition, it was found that transplantation of NPM-ALK-transduced BM cells into IL-9 transgenic mice results in the generation of various lymphoid and plasmacytoid tumors [61].…”