T-CELL RECEPTOR GENE REARRANGEMENT IN CANINE MYCOSIS-FUNGOIDES - FURTHER SUPPORT FOR A CANINE MODEL OF CUTANEOUS T-CELL LYMPHOMA

Canine cutaneous T-cell lymphoma (CTCL) is a morphologic and immunophe notypic simulant of human mycosis fungoides (MF) characterized by an i nfiltrate of atypical, hyperconvoluted, epidermotropic T cells. To fur ther support our hypothesis that canine MF is a useful model for the s tudy of human CTCL, we have used Southern blotting to search for clona l T-cell proliferations in canine MF. Cellular DNA was extracted from normal dog buffy coat cells (n = 8), lesional canine MF skin (n = 8), canine MF buffy coat cells (n = 7), normal dog skin (n = 3), and norma l human buffy coat cells (n = 5), digested with a panel of restriction enzymes and Southern blotted onto nylon membranes. All cases of canin e MF were also immunophenotyped with anti-canine monoclonal antibodies to CD4, CD8, CD18, CD45RA, canine class II, T-cell activation antigen s, and pan-B-cell antigens. Normal dogs gave reproducible digestion pa tterns in blood and skin, which differed from the human germline patte rns when probed with a human T-cell receptor (TCR), beta chain constan t region (C beta) cDNA. Common germline bands between the species incl uded the 3.5-kb Eco RI, 3.4-kb Bam HI, 5.4-kb Sac I. These results con firmed that the TCR-beta gene is evolutionarily conserved between dog and man. Immunostaining revealed that 3/7 cases were CD4+ canine CTCL and 4/7 were CD8+ canine CTCL. Rearranged bands, deletion of germline bands, as well as minor alterations in electrophoretic mobility were o bserved in lesional DNA from seven of eight cases of canine MF, with a t least two restriction digests in each case. Dog rearrangements were best detected with Bgl II, Eco RI, Eco RV, and Sac I, whereas deletion s were detected with Bgl II, Sac I, Eco RV, and Bam HI. These studies demonstrate the presence of clonal TCR rearrangement in canine MF, fur ther supporting the similarity of this tumor to human MF and its role as an animal model of CTCL.