[Large granular lymphocyte leukemia].

Large granular lymphocyte leukemia (LGLL) is defined as clonal proliferation of LGLs in peripheral blood. The following studies were conducted to address some issues in chronic LGLL. (1) Chronic LGLL is characterized by the indolent course, and the diagnosis of leukemia is difficult in such patients as those without distinct organomegaly and/or any evidence of monoclonality. We performed immunohistological studies in a patient with persistent NK lymphocytosis. No organomegaly had been seen in the patient during a three-year-observation, who died from cerebrovascular accident. The autopsy findings revealed multi-organ infiltration including spleen, liver, bone marrow, lymph nodes and lung. These findings suggest that the cells of chronic LGLL have infiltrative capacity characteristic of malignant cells. (2) Lymphocytosis in chronic LGLL is usually stable for a long period. We found that both T- and NK-LGLL cells strongly expressed CD95, an apoptosis related protein. Anit-CD95 did not induce apoptosis, but suppressed proliferation induced by IL-2 or anti-CD3. These results suggest that CD95-CD95 ligand system is involved in the slow cell growth characteristic of chronic LGLL. (3) CD4+CD8+ double positive (DP) cases are rarely seen in LGLL, and the physiologic counterpart of the leukemic cells has not been determined yet. We found that the DP-LGLL had alpha alpha type in the CD8 subunit and did not express RAG-1, these findings being characteristic of peripheral T cells. We also found that they expressed IL-4 mRNA and secreted IL-4 on activation. These results strongly suggest that DP-T-LGLL represents an expansion of a rare subset of peripheral DP-T cells, possibly derived from IL-4 activated CD4 single positive T cells.