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

Exp Hematol. 1998 Mar;26(3):188-97.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • B7-1 Antigen / metabolism
  • B7-2 Antigen
  • Chromosome Aberrations / genetics
  • Chromosome Disorders
  • Fusion Proteins, bcr-abl / genetics*
  • Fusion Proteins, bcr-abl / metabolism
  • Genes, p53
  • Humans
  • Karyotyping
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia-Lymphoma, Adult T-Cell / genetics*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Transgenic*
  • Phosphotyrosine / metabolism
  • Point Mutation
  • Polymorphism, Single-Stranded Conformational
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / metabolism
  • Trisomy
  • Tumor Cells, Cultured*

Substances

  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CD86 protein, human
  • Cd86 protein, mouse
  • Membrane Glycoproteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Phosphotyrosine
  • Fusion Proteins, bcr-abl