Honda H, Ohno S, Takahashi T, Takatoku M, Yazaki Y, Hirai H
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Exp Hematol. 1998 Mar;26(3):188-97.
The p210bcr/abl chimeric protein is implicated in the pathogenesis of Philadelphia chromosome-positive human leukemias. Previously, we generated transgenic mice expressing p210bcr/abl by the metallothionein enhancer/promoter (MT/p210bcr/abl) and observed that these mice reproducibly developed T cell leukemia. In this report, we describe the establishment, characterization, and chromosomal analysis of two novel leukemic cell lines derived from MT/p210bcr/abl leukemic mice. Both cell lines carried the transgene and showed the same gene rearrangement patterns as observed in the parental leukemic cells. Expression, tyrosine-phosphorylation, and enhanced kinase activity of the p210bcr/abl were also detected. RT-PCR/SSCP for p53 transcript revealed that one of the cell lines carried a mutation, in contrast to the normal pattern shown by the parental leukemic cells. In addition, the other cell line showed a karyotype of trisomy 15. These results suggest that the p53 mutation and chromosomal abnormality may confer a proliferative ability on leukemic cells in vitro. These new cell lines are considered to be a valuable model not only for examining the biologic properties of p210bcr/abl but also for investigating the malignant process that promotes the proliferation of the leukemic cells expressing p210bcr/abl. Furthermore, these cell lines could be used in therapeutic studies, including adoptive immunotherapy.
p210bcr/abl嵌合蛋白与费城染色体阳性人类白血病的发病机制有关。此前，我们通过金属硫蛋白增强子/启动子（MT/p210bcr/abl）生成了表达p210bcr/abl的转基因小鼠，并观察到这些小鼠可重复性地发生T细胞白血病。在本报告中，我们描述了从MT/p210bcr/abl白血病小鼠衍生的两种新型白血病细胞系的建立、特征及染色体分析。两种细胞系均携带转基因，并显示出与亲代白血病细胞中观察到的相同基因重排模式。还检测到了p210bcr/abl的表达、酪氨酸磷酸化及增强的激酶活性。对p53转录本进行的RT-PCR/SSCP显示，其中一个细胞系携带突变，这与亲代白血病细胞显示的正常模式不同。此外，另一个细胞系显示出15号染色体三体的核型。这些结果表明，p53突变和染色体异常可能赋予白血病细胞体外增殖能力。这些新的细胞系不仅被认为是用于研究p210bcr/abl生物学特性的有价值模型，也是用于研究促进表达p210bcr/abl的白血病细胞增殖的恶性过程的有价值模型。此外，这些细胞系可用于治疗研究，包括过继性免疫治疗。
