PERIPHERAL T-CELL LYMPHOMA IN LCK(PR)-BCL-2 TRANSGENIC MICE

t(14;18) is the most common translocation in human lymphoid malignancy and results in bcl-2 overexpression, bcl-2 blocks apoptosis and constitutes the initial member of a new catagory of oncogenes, ie, regulators of cell death. Bcl-2-lg transgenic mice develop follicular hyperplasia and progress to malignant B-cell lymphoma. To assess the oncogenic potential of bcl-2 in the T-cell lineage, a cohort of 68 lck(pr)-bcl-2 transgenic mice and 56 control littermates were monitored for signs of malignancy over a 24-month period. Eighteen (26%) lck(pr)-bcl-2 mice developed diffuse, predominantly large-cell lymphomas at a mean age of 18 months. In contrast, only one nontransgenic control mouse developed lymphoma. CD3 surface expression and clonal T-cell receptor beta rearrangements support the T-lineage classification of these neoplasms, lck(pr-)bcl-2-enforced lymphomas are predominantly CD4(+)CD8(-), consistent with a mature peripheral T-cell phenotype. These data provide support for the thesis that violation of homeostasis through the repression of cell death can be a primary mechanism of tumorigenesis in multiple lineages. (C) 1995 by The American Society of Hematology.