Hagenbeek A, Martens A C, Colly L P
Semin Oncol. 1987 Jun;14(2 Suppl 1):202-6.
The in vivo development of an ara-C-resistant leukemic cell line is reported in a rat leukemia model (BNML) that is generally accepted as a relevant model for human acute myelocytic leukemia. It took 32 continuous leukemia transplant generations, performed over 20 months, and a total dose of 28.5 g ara-C/kg to induce complete resistance. Preliminary data indicate that the development of ara-C resistance is related with decreased intracellular levels of deoxycytidine kinase. Deoxycytidine deaminase levels were not increased. Thus this enzyme does not seem to be involved with induction of resistance. This preclinical rat model for human AML provides a solid basis for studies in depth on the mechanism(s) and possible prevention and effective treatment of resistance to ara-C.
在大鼠白血病模型（BNML）中报道了阿糖胞苷耐药白血病细胞系的体内发育情况，该模型通常被认为是人类急性髓细胞白血病的相关模型。诱导完全耐药需要连续进行32代白血病移植，历时20个月，阿糖胞苷的总剂量达28.5 g/kg。初步数据表明，阿糖胞苷耐药的发生与脱氧胞苷激酶细胞内水平降低有关。脱氧胞苷脱氨酶水平并未升高。因此，该酶似乎与耐药诱导无关。这种人类急性髓细胞白血病的临床前大鼠模型为深入研究阿糖胞苷耐药的机制、可能的预防措施及有效治疗方法提供了坚实的基础。
