Disseminated growth of a human multiple myeloma cell line in mice with severe combined immunodeficiency disease.

We have successfully engrafted a human multiple myeloma cell line, ARH-77, into C.B. 17 SCID mice. When ARH-77 cells were injected s.c., tumors grew only at the site of inoculation (five of five). When ARH-77 cells were injected i.v. tumors did not grow in any of the mice (zero of five). However, when mice were given gamma-irradiation with 150 rads and then inoculated i.v. with 10(7) ARH-77 cells, 100% (13 of 13) of the mice developed tumors. Hind leg paralysis was observed in 13 of 16 mice as a result of compression of the spinal cord by tumor. Histological analysis demonstrated that myeloma cells proliferated and formed osteolytic lesions (15 of 16) in the vertebrae and bones of the skull (14 of 16). Tumor cells also invaded the brain and meninges (14 of 16), lung (13 of 15), liver (seven of 15), and kidney (two of 15). Flow cytometric analysis demonstrated that the phenotype of 31% of the bone marrow cells in the vertebrae and 79% of s.c. tumor cells was similar to ARH-77 cells (CD38+, PCA-1+, HLA-Classes 1 and II+). Furthermore, DNA hybridization with a human AluI probe confirmed their human origin. ARH-77-derived human immunoglobulin was detected in the serum of SCID/ARH-77 mice by ELISA. These observations demonstrate systemic involvement of human multiple myeloma following i.v. injection of ARH-77 cells into irradiated mice. This in vivo model should be useful for evaluating new therapeutic modalities for myeloma.