化疗药物联合细胞因子对bcr-abl转基因小鼠骨髓细胞生长及转基因表达的影响

Influence of chemotherapeutants and cytokines on growth and transgene expression of bone marrow cells from MT/p210(bcr abl) transgenic mice

应用Ｈｕ或５Ｆｕ和鼠干细胞因子（ｍＳＣＦ）及鼠白细胞介素３（ｍＩＬ３）培养含金属硫蛋白（ＭＴ）启动子和增强子序列、ｂｃｒａｂｌｃＤＮＡ（ｐ２１０）序列及ＳＶ４０剪切和Ｐｏｌｙ（Ａ）信号序列的转基因慢粒白血病小鼠骨髓细胞，观察化疗药物及细胞因子单独或联合应用对ＭＴ／ｐ２１０（ｂｃｒａｂｌ）转基因小鼠骨髓细胞生长的影响，并采用ＲＴＰＣＲ分析培养前后骨髓细胞中转基因的表达。结果表明，ｍＳＣＦ和ｍＩＬ３联合应用时，明显促进骨髓细胞增殖及集落形成；不加细胞因子培养，则细胞增殖和转基因表达均受抑制；Ｈｕ或５Ｆｕ与ｍＳＣＦ及ｍＩＬ３联合应用时，同样抑制细胞增殖及转基因表达。提示联合应用化疗药物及细胞因子治疗ＣＭＬ是具有极好应用前景的策略。

The bone marrow cells of CML(chronic myelogenous leukemia) transgenic mice carrying metallothionein(MT) promoter/enhancer, bcr abl(p210) cDNA and SV40 splicing/poly(A) signal sequences were cultured in liquid and soft agar with hydroxyurea(Hu), 5 fluorouracil(5 Fu), mouse stem cell factor(mSCF) and mouse interleukin 3(mIL 3) independently or combinatively. The cell or colony counting and transgene RT PCR analysis showed that the proliferation, colony formation and transgene expression of the bone marrow cells were advanced in the combinative culture of mSCF with mIL 3, but they were significantly inhibited in the culture without any growth factors, or with mSCF, mIL 3 and Hu or 5 Fu. These findings suggest that the combinative utilization of chemotherapeutants and cytokines is a potentially effective strategy of the clinical treatment for CML.