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[Large granular lymphocyte leukemia]
M Mizuki1, S Tagawa, M Shibano
1Department of Hematology and Oncology, Osaka University Medical School, Suita.
Insights
Large granular lymphocyte leukemia (LGLL) involves clonal LGL proliferation. Studies reveal LGLL cells infiltrate organs, CD95 influences slow growth, and DP-T-LGLL may arise from IL-4 activated T cells.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Large granular lymphocyte leukemia (LGLL) is a clonal proliferation of large granular lymphocytes (LGLs) in peripheral blood.
- Chronic LGLL often presents indolently, posing diagnostic challenges due to lack of distinct organomegaly or monoclonality evidence.
Observation:
- Immunohistological studies in a persistent NK lymphocytosis patient revealed multi-organ infiltration upon autopsy, despite no apparent organomegaly during a three-year observation period.
- Both T- and NK-LGLL cells expressed CD95, an apoptosis-related protein, with anti-CD95 suppressing IL-2 or anti-CD3 induced proliferation.
- CD4+CD8+ double positive (DP) LGLL cases, rare in LGLL, exhibited alpha alpha CD8 subunit type, lacked RAG-1 expression, and secreted IL-4, characteristic of peripheral T cells.
Findings:
- Chronic LGLL cells demonstrate infiltrative capacity, characteristic of malignant cells.
- The CD95-CD95 ligand system appears to regulate the slow cell growth typical of chronic LGLL.
- DP-T-LGLL likely represents an expansion of a rare peripheral DP-T cell subset, potentially originating from IL-4 activated CD4+ T cells.
Implications:
- Findings highlight the infiltrative potential of chronic LGLL cells, necessitating careful monitoring.
- Understanding the CD95 pathway's role in LGLL proliferation offers potential therapeutic targets.
- Identifying the origin of DP-T-LGLL provides insights into T-cell subsets and their role in leukemia development.
Abstract:
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.