Establishment, characterization, and chromosomal analysis of new leukemic cell lines derived from MT/p210bcr/abl...

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.