Houghton P J, Mirro J, Goorha R M, Raimondi S C, Fridland A, Houghton J A
Department of Biochemical, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Cancer Res. 1989 Dec 15;49(24 Pt 1):7124-31.
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.
研究了在通过不同技术免疫剥夺的小鼠以及CD-nu/nu无胸腺小鼠中人类CCRF-CEM T细胞淋巴母细胞白血病的生长情况。雌性CBA/CaJ小鼠通过婴儿胸腺切除术进行免疫剥夺，在全身照射（925 cGy）前48小时用1-β-D-阿拉伯呋喃糖基胞嘧啶（200 mg/kg）进行预处理，称为θara-Cγ；或者在胸腺切除术后，小鼠接受925 cGy全身照射并进行骨髓重建（4×10⁶个有核细胞），称为θγBM。只有在通过θγBM免疫剥夺的小鼠中，在移植CCRF-CEM前18 - 24小时给予单剂量环磷酰胺（100 mg/kg），才会出现渐进性可重复的植入和肿瘤生长。以这种方式免疫剥夺的小鼠，肿瘤植入率为100%，且80%的肿瘤在46天内达到大于或等于1 cm³。在免疫剥夺的CBA/CaJ小鼠中，但不是在CD-nu/nu无胸腺小鼠中，移植到皮下部位的肿瘤转移至主动脉旁和腋窝淋巴结。通过免疫表型分析和核型分析证实了肿瘤向淋巴结的转移扩散。与培养中的CCRF-CEM细胞不同，培养中的CCRF-CEM细胞表达细胞质CD3（T3）但不表达表面CD3，皮下和转移的CCRF-CEM细胞系在体外暴露于佛波醇-12-肉豆蔻酸酯13-乙酸酯以模拟异种移植细胞中发生的明显分化，处理后可见表面CD3的类似表达。CD3的这种表面表达伴随着T细胞受体α链mRNA的产生和T细胞受体的表面表达。在体外的CCRF-CEM细胞系和体内的异种移植细胞中发现了相同的T细胞受体β和γ链基因重排，表明只存在一个克隆，且免疫表型分析的差异不是克隆选择的结果。这些结果表明宿主（小鼠）造血因子可能影响人类白血病细胞的分化。
