title: Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia.
abstract: Chronic T lymphoid leukemias are defined as leukemias of post-thymic T cells. The CD4+CD8+ double-positive (DP) phenotype is seen in a few cases. Since DP generally occurs in thymic T cells, whether the DP T leukemia cells represent thymic or peripheral T cells has been a matter of controversy. To address this issue, we studied phenotypical features in eight cases of DP T cell leukemia. Thymic DP T cells and peripheral CD8+ T cells have CD8 of alphabeta subunit, while CD8alphaalpha is induced in CD4+ T cells on activation with IL-4. We found that two patients with DP T large granular lymphocyte leukemia (LGLL) showed dim expression of CD8alphaalpha, identical to the phenotype on IL-4-activated DP-T cells. The leukemic cells of these patients expressed IL-4 mRNA and produced high levels of IL-4. These findings suggest that they may be derived from peripheral CD4+ T cells. Three patients with adult T cell leukemia/lymphoma (ATLL) showed CD8alphaalpha, suggestive of an activated peripheral T cell origin. One case expressed CD8alphaalpha dim and IL-4 mRNA, while the other two cases expressed no IL-4 mRNA and showed CD8alphaalpha bright phenotype, features not found in normal T cell populations. Three patients with T-prolymphocytic leukemia (T-PLL) expressed CD8alphabeta. The DP phenotype is relatively common in T-PLL, and CD4+CD8alphabeta+ is characteristic 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 the late stage of thymic T cell development. On the basis of these findings, we propose a late thymic origin for DP T-PLL. The phenotype of DP T cells differed for each entity and appeared to correlate with minor normal DP T cell population.
authors.affiliation: Department of Hematology and Oncology, Osaka University Medical School, Suita, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mizuki
authors.forename: S
authors.initials: S
authors.lastname: Tagawa
authors.forename: T
authors.initials: T
authors.lastname: Machii
authors.forename: M
authors.initials: M
authors.lastname: Shibano
authors.forename: E
authors.initials: E
authors.lastname: Tatsumi
authors.forename: K
authors.initials: K
authors.lastname: Tsubaki
authors.forename: H
authors.initials: H
authors.lastname: Tako
authors.forename: A
authors.initials: A
authors.lastname: Yokohama
authors.forename: S
authors.initials: S
authors.lastname: Satou
authors.forename: J
authors.initials: J
authors.lastname: Nojima
authors.forename: T
authors.initials: T
authors.lastname: Hirota
authors.forename: T
authors.initials: T
authors.lastname: Kitani
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000096:biosynthesis; D015461:Leukemia, Prolymphocytic, T-Cell / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D010641:Phenotype
chemical_list: D015847:Interleukin-4