BCR-ABL and v-abl oncogenes induce distinct patterns of thymic lymphoma involving different lymphocyte subsets

J Virol. 1993 Oct;67(10):6033-46. doi: 10.1128/JVI.67.10.6033-6046.1993.

Abstract

The human BCR-ABL oncogenes encoded by the Philadelphia chromosome (Ph) affect the pathogenesis of diverse types of leukemia and yet are rarely associated with T-lymphoid leukemia. To determine whether BCR-ABL kinases are inefficient in transforming T lymphocytes, BCR-ABL-expressing retroviruses were injected intrathymically into mice. Thymomas that expressed BCR-ABL kinase developed after a relatively long latent period. In most thymomas, deletion of 3' proviral sequences resulted in loss of tk-neo and occasionally caused expression of kinase-active carboxy-terminally truncated BCR-ABL oncoprotein. In contrast, deletion of 3' proviral sequences was not observed in thymomas induced with Abelson murine leukemia virus (A-MuLV). BCR-ABL viruses induced distinct patterns of disease and involved different thymocyte subsets than A-MuLV and Moloney murine leukemia virus (Mo-MuLV). While Mo-MuLV only induced Thy-1+ thymomas, v-abl- and BCR-ABL-induced thymomas often contained mixed populations of B220+ and Thy-1+ lymphocytes in the same tumor. In most v-abl and BCR-ABL tumors, Thy-1+ lymphoid cells expressed CD8 and a continuum of CD4 ranging from negative to positive. Conversely, Mo-MuLV thymomas contained distinct populations of CD4+ cells that were either CD8+ or CD8-. A-MuLV-transformed T-lymphoid cells did not express the CD3/T-cell receptor complex, while BCR-ABL tumors were CD3+. Thus, BCR-ABL viruses preferentially induce somewhat more differentiated T lymphocytes than are transformed by A-MuLV. Furthermore, rare B220+ lymphocytes may represent preferred v-abl and BCR-ABL transformation targets in the thymus.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / analysis
  • CD3 Complex / analysis
  • CD4 Antigens / analysis
  • CD8 Antigens / analysis
  • Cell Transformation, Neoplastic*
  • Flow Cytometry
  • Fusion Proteins, bcr-abl / genetics*
  • Gene Deletion
  • Genes, Immunoglobulin
  • Genes, abl*
  • Humans
  • Leukemia Virus, Murine / genetics
  • Mice
  • Oncogenes*
  • Philadelphia Chromosome
  • Proviruses / genetics
  • Receptors, Antigen, T-Cell / genetics
  • Repetitive Sequences, Nucleic Acid
  • Restriction Mapping
  • Retroviridae / genetics*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / physiology*
  • Thymoma / genetics*
  • Thymoma / microbiology
  • Thymus Neoplasms / genetics*
  • Thymus Neoplasms / microbiology
  • Transcription, Genetic

Substances

  • Antigens, CD
  • CD3 Complex
  • CD4 Antigens
  • CD8 Antigens
  • Receptors, Antigen, T-Cell
  • Fusion Proteins, bcr-abl