PHENOTYPICAL HETEROGENEITY OF CD4(-POSITIVE CHRONIC-T-LYMPHOID LEUKEMIA()CD8(+) DOUBLE)

Chronic T lymphoid leukemias are defined as leukemias of post-thymic T cells. The CD4(+)CD8(+) double-positive (DP) phenotype is seen in a f ew cases. Since DP generally occurs in thymic T cells, whether the DP T leukemia cells represent thymic or peripheral T cells has been a mat ter of controversy. To address this issue, we studied phenotypical fea tures in eight cases of DP T cell leukemia. Thymic DP T cells and peri pheral CD8(+) T cells have CD8 of alpha beta subunit, while CD8 alpha alpha is induced in CD4(+) T cells on activation with IL-4. We found t hat two patients with DP T large granular lymphocyte leukemia (LGLL) s howed dim expression of CD8 alpha alpha, identical to the phenotype on IL-4-activated DP-T cells. The leukemic cells of these patients expre ssed IL-4 mRNA and produced high levels of IL-4. These findings sugges t that they may be derived from peripheral CD4(+) T cells. Three patie nts with adult T cell leukemia/lymphoma (ATLL) showed CD8 alpha alpha, suggestive of an activated peripheral T cell origin. One case express ed CD8 alpha alpha dim and IL-4 mRNA, while the other two cases expres sed no IL-4 mRNA and showed CD8 alpha alpha bright phenotype, features not found in normal T cell populations. Three patients with T-prolymp hocytic leukemia (T-PLL) expressed CD8 alpha beta. The DP phenotype is relatively common in T-PLL, and CD4(+)CD8 alpha beta(+) is characteri stic of thymic T cells. The DP T-PLL cells did not express TdT,CD1 or recombination activating gene-1 (RAG-1), which is down-regulated at th e late stage of thymic T cell development. On the basis of these findi ngs, we propose a late thymic origin for on T-PLL. The phenotype of DP T cells differed for each entity and appeared to correlate with minor normal DP T cell population.