IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENES IN T-LYMPHOID MALIGNANCIES IN AN ANIMAL-MODEL SYSTEM

The molecular events characterizing lymphoid malignancy have been exam ined in an animal model system, specifically, the retroviral induction of leukemia and lymphoma in the domestic cat following infection with feline leukemia virus (FeLV). Genes differentially expressed in FeLV- induced lymphomas were isolated using a strategy of differential hybri dization. Six genes were identified which demonstrate a higher level o f expression in an FeLV-induced feline thymic tumor as compared with n ormal thymus. The differentially expressed genes encode the feline hom ologues of ribosomal proteins S3a, S4, S17, and L41, elongation factor -1 alpha, and cytochrome oxidase sub-unit I. Northern-blot analysis an d quantification by phosphorimaging demonstrates that these genes are expressed at levels from 1.5- to 3.1-fold higher in J5-1 thymic tumor as compared with normal thymus. Expression of the selected ribosomal p rotein mRNA was further examined in a series of human and feline tissu es, including normal tissues, malignant tumors and cell lines. Our dat a reveal that elevation of the selected ribosomal protein mRNA is asso ciated with all FeLV-induced thymic lymphomas examined. The differenti ally expressed ribosomal protein mRNA accumulates in a balanced manner in thymic lymphomas. By contrast, the elevation in ribosomal protein mRNA levels is not associated uniformly with hematopoietic malignancy, T-lymphoid malignancy, solid tumors or actively proliferating cells. Rather, the elevation appears to be a uniform and distinctive feature of T-cell malignancy of this particular type. The elevated expression of these genes may be causally related to the neoplastic process. (C) 1995 Wiley-Liss, Inc.