Growth and differentiation of a human T-cell leukemia cell line, CCRF-CEM, grafted in mice
Houghton, P.J.; Mirro, J.; Goorha, R.M.; Raimondi, S.C.; Fridland, A.; Houghton, J.A.
Cancer Research 49(24 Part 1): 7124-7131
1989
ISSN/ISBN: 0008-5472 PMID: 2555061 Document Number: 331783
The growth of human CCRF-CEM T-cell lymphoblastic leukemia was studied in mice immune deprived by different techniques, and in CD-nu/nu athymic mice. Female CBA/CaJ mice were immune deprived by infant thymectomy, priming with 1-beta-D-arabinofuranosylcytosine (200 mg/kg) 48 h prior to total body irradiation (925 cGy) designated theta ara-C gamma; or after thymectomy the mice received 925 cGy total body irradiation with marrow reconstitution (4 x 10(6) nucleated cells), designated theta gamma BM. Only in mice immune deprived by theta gamma BM, subsequently given a single dose of cyclophosphamide (100 mg/kg) 18-24 h before transplantation of CCRF-CEM, was there progressive reproducible engraftment and tumor growth. For mice immune deprived in this manner the tumor engraftment rate was 100 and 80% of tumors achieved greater than or equal to 1 cm3 within 46 days. In immune-deprived CBA/CaJ mice, but not CD-nu/nu athymic mice, tumor transplanted to the s.c. site metastasized to paraaortic and axillary nodes. Metastatic spread to lymph nodes was confirmed by immunophenotyping and by karyotyping. In contrast to the CCRF-CEM cells in culture, which expressed cytoplasmic CD3 (T3) but not surface CD3, both s.c. and metastatic CCRF-CEM line was exposed to phorbol-12-myristate 13-acetate in vitro to mimic the apparent differentiation which occurred in the xenografted cells, and a similar expression of surface CD3 after treatment was seen. This surface expression of CD3 was accompanied by production of mRNA for the T-cell receptor alpha chain and surface expression of the T-cell receptor. Identical T-cell receptor beta and gamma chain gene rearrangements were found for the CCRF-CEM line in vitro and the xenografted cells in vivo, demonstrating that only one clone was present and that differences in immunophenotyping were not the result of clonal selection. These results suggest that host (mouse) hematopoietic factors could affect human leukemic cell differentiation.