Growth and Differentiation of a Human T-Cell Leukemia Cell Line, CCRF-CEM, Grafted in Mice

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-β-D-arabinofuranosylcytosine (200 mg/kg) 48 h prior to total body irradiation (925 cGy) designated θara-Cϒ or after thymectomy the mice received 925 cGy total body irradiation with marrow reconstitution (4 × 106 nucleated cells), designated θϒBM. Only in mice immune deprived by θϒBM, 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 >1 cm3 within 46 days. In immunedeprived 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 cells xenografted in mice expressed surface CD3. The 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 a chain and surface expression of the T-cell receptor. Identical T-cell receptor β and ϒ 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.