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Non-malignant leukocytes delay spontaneous B-CLL cell apoptosis
R Gamberale1, J Geffner, G Arrosagaray
1Laboratory of Immunology, Institute of Haematologic Research, National Academy of Medicine, Buenos Aires, Argentina.
Leukemia
|December 26, 2001
Summary
Accessory leukocytes, including monocytes and NK cells, prolong chronic lymphocytic leukemia (B-CLL) cell survival in vitro by delaying apoptosis. This suggests a role for these cells in B-CLL progression in vivo.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- Malignant B cells in chronic lymphocytic leukemia (B-CLL) exhibit prolonged survival in vivo but undergo spontaneous apoptosis in culture.
- Understanding the factors that regulate B-CLL cell survival is crucial for elucidating disease pathogenesis.
Purpose of the Study:
- To investigate the role of accessory leukocytes in modulating the apoptosis of B-CLL cells in an in vitro setting.
- To identify specific leukocyte populations responsible for influencing B-CLL cell survival.
Main Methods:
- Long-term cultures of total mononuclear cells (TMC) from B-CLL patients were established.
- Cultures were also performed with B-CLL cells depleted of monocytes, NK cells, and T lymphocytes.
- Flow cytometry was used to analyze protein expression (Bcl-2, Fas, Fas ligand).
Main Results:
- Accessory leukocytes significantly prolonged the survival of B-CLL cells in all patients studied (n=25).
- Monocytes and, to a lesser extent, NK cells were identified as the primary mediators of this anti-apoptotic effect, partly via soluble factors.
- The protective effect correlated with delayed down-regulation of Bcl-2 expression on B-CLL cells.
Conclusions:
- Monocytes and NK cells play a significant role in inhibiting B-CLL cell apoptosis in vitro.
- These findings suggest that accessory leukocytes may contribute to the accumulation of leukemic cells in chronic lymphocytic leukemia patients in vivo.