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 rar ely associated with T-lymphoid leukemia. To determine whether BCR-ABL kinases are inefficient in transforming T lymphocytes, BCR-ABL-express ing retroviruses were injected intrathymically into mice. Thymomas tha t expressed BCR-ABL kinase developed after a relatively long latent pe riod. In most thymomas, deletion of 3' proviral sequences resulted in loss of tk-neo and occasionally caused expression of kinase-active car boxy-terminally truncated BCR-ABL oncoprotein. In contrast, deletion o f 3' proviral sequences was not observed in thymomas induced with Abel son murine leukemia virus (A-MuLV). BCR-ABL viruses induced distinct p atterns of disease and involved different thymocyte subsets than A-MuL V and Moloney murine leukemia virus (Mo-MuLV). While Mo-MuLV only indu ced Thy-1+ thymomas, v-abl- and BCR-ABL-induced thymomas often contain ed 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 CD 8 and a continuum of CD4 ranging from negative to positive. Conversely , Mo-MuLV thymomas contained distinct populations of CD4+ cells that w ere either CD8+ or CD8-. A-MuLV-transformed T-lymphoid cells did not e xpress the CD3/T-cell receptor complex, while BCR-ABL tumors were CD3. Thus, BCR-ABL viruses preferentially induce somewhat more differenti ated T lymphocytes than are transformed by A-MuLV. Furthermore, rare B 220+ lymphocytes may represent preferred v-ab/ and BCR-ABL transformat ion targets in the thymus.