Establishment, characterization, and chromosomal analysis of new leukemic cell lines derived from MT/p210bcr/abl transgenic mice.
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.
Honda
H
H
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Ohno
S
S
Takahashi
T
T
Takatoku
M
M
Yazaki
Y
Y
Hirai
H
H
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism; D016158:Genes, p53; D006801:Humans; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D019000:Phosphotyrosine / Q000378:metabolism; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D014314:Trisomy; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019000:Phosphotyrosine; D016044:Fusion Proteins, bcr-abl