Ss. Clark et al., BCR-ABL AND V-ABL ONCOGENES INDUCE DISTINCT PATTERNS OF THYMIC LYMPHOMA INVOLVING DIFFERENT LYMPHOCYTE SUBSETS, Journal of virology, 67(10), 1993, pp. 6033-6046
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.