BCR-ABL and v-abl oncogenes induce distinct patterns of thymic lymphoma involving different lymphocyte subsets.
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.
Department of Human Oncology, University of Wisconsin, Madison 53792.
S S
SS
Clark
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E
Chen
M
M
Fizzotti
O N
ON
Witte
V
V
Malkovska
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002471:Cell Transformation, Neoplastic; D005434:Flow Cytometry; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D017353:Gene Deletion; D005803:Genes, Immunoglobulin; D016313:Genes, abl; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics; D051379:Mice; D009857:Oncogenes; D010677:Philadelphia Chromosome; D011533:Proviruses / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D012190:Retroviridae / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology*; D013945:Thymoma / Q000235:genetics* / Q000382:microbiology; D013953:Thymus Neoplasms / Q000235:genetics* / Q000382:microbiology; D014158:Transcription, Genetic
D015703:Antigens, CD; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell; D016044:Fusion Proteins, bcr-abl