全反式维甲酸诱导急性早幼粒细胞白血病细胞分化为树突状细胞的实验研究  

Induction of Dendritic Cells Derived from Acute Promyelocytic Leukemia Cells by All Trans Retinoic Acid

作　　者：田发青[1] 张连生[1] 王春燕[1] 陶维国[1] 

机构地区：[1]兰州大学第二医院血液肿瘤科

出　　处：《中国实验血液学杂志》2008年第5期1140-1145,共6页Journal of Experimental Hematology

摘　　要：全反式维甲酸(ATRA)诱导APL细胞分化为成熟树突状细胞(dendritic cell,DC),目前国内外鲜见报道。本研究探讨全反式维甲酸与经典细胞因子共同作用诱导急性早幼粒细胞白血病(APL)细胞分化为DC的可能性,为研制APL-DC疫苗提供新的方法。对初治APL患者骨髓单个核细胞及HL-60细胞株分别在完全培养液中培养,用经典细胞因子组合(GM-CSF、IL-4、TNF-α)共处理,ATRA只在实验组加用。观测细胞形态,检测DC免疫表型,测定上清液IL-12水平,观察MLR反应及CTL效应。结果表明:实验组所得细胞有较明显树突状突起,有APL遗传学特征,其CD1a、CD83、CD80、CD86、HLA-DR和CD1d表达及IL-12分泌水平明显增高,并具有明显的MLR反应及CTL效应,但在HL60-DC中,CD1a增加无统计学差异。结论:利用ATRA可以成功诱导APL细胞为成熟功能性DC,其介导的MLR及CTL效应明显。经ATRA组合诱导的树突状细胞CD1d表达明显增高,推测可能参与NKT细胞激活,具体机制需进一步研究。This study was purposed to investigate the possibility of differentiating the acute promyelocytic leukemia （APL） cells into dendritic cells （DCs） induced by all-trans retinoic acid （ATRA） combined with classic cytokines so as to provide a new approach for development of APL-DC vaccine. The bone marrow mononuclear cells from a new diagnosed patient with APL and HL-60 cells were separately cultured in complete culture medium. The ceils were treated by ATRA, GM-CSF, IL-4 and TNFα in experimental groups and no ATRA was added in control and blank control groups. The cell morphology was observed by light microscopy, the phenotypes of DCs were detected by flow cytometry, the level of IL-12 was measured by using ELISA, the mixed lymphocyte reaction （MLR） and effect of cytotoxic T-lymphocyte （CTL） were assayed by MTT method. The results indicated that in experiment groups, the cells had dendritic appearence and cytogenetic characteristics of APL; expression of CD1 a, CD83, CD80, CD86, HLA-DR and CDld as well as level of IL-12 obviously increased; the MLR and CTL effects were significant, but increase of CDla expression in HL60-DCs did not show statistical difference from control and blank control groups. It is concluded that ATRA can successfully induce APL cells to differentiate into functionally mature DSs which obviouly mediate MLR and CTL effects. The APL-DCs derived by ATRA can notably express CDld that may activate CDld-restricted NKT cells and promote proliferation of NRT cells. The exact mechanism of which should be furtherly studied.

关 键 词：全反式维甲酸 急性早幼粒细胞白血病细胞 HL-60细胞 树突状细胞 CD1D 

分 类 号：R73-362[医药卫生—肿瘤]