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An anti-apoptotic role for galectin-3 in diffuse large B-cell lymphomas
Katrina K Hoyer1, Mabel Pang, Dorina Gui
1Department of Pathology and Laboratory Medicine, University of California at Los Angeles School of Medicine, Los Angeles, California 90095-1732, USA.
The American Journal of Pathology
|February 26, 2004
Summary
Galectin-3, an anti-apoptotic protein, is highly expressed in certain B-cell lymphomas like diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM), promoting cell survival. Its absence in other lymphomas suggests a role in specific B-cell neoplasm development.
Area of Science:
- Molecular Biology
- Cancer Biology
- Immunology
Background:
- Resistance to apoptosis is crucial for lymphomagenesis.
- Aberrant expression of cell survival proteins like BCL-2 and c-MYC is observed in lymphoma subtypes.
- Galectin-3 is an anti-apoptotic protein protecting various cell types from death.
Purpose of the Study:
- To investigate the role of galectin-3 expression in B-cell neoplasms.
- To determine if galectin-3 confers resistance to apoptosis in B cells.
- To correlate galectin-3 expression patterns with B-cell development and lymphoma subtypes.
Main Methods:
- Analysis of galectin-3 protein expression in various B-cell lymphoma cell lines and patient samples (DLBCL, PEL, MM, BL, FL, MZL, MALT, B-SLL).
- Transfection of galectin-3-negative Burkitt lymphoma (BL) cells with a galectin-3 expressing plasmid.
- Transfection of galectin-3-positive Primary Effusion Lymphoma (PEL) cells with a truncated galectin-3 vector.
- Assessment of apoptosis resistance using anti-Fas-induced cell death assays.
- Examination of galectin-3 expression during normal B-cell development.
Main Results:
- High galectin-3 protein levels were detected in diffuse large B-cell lymphoma (DLBCL), primary effusion lymphoma (PEL), and multiple myeloma (MM) cell lines and patient samples.
- Galectin-3 was not detected in Burkitt lymphoma (BL), follicular lymphoma (FL), marginal zone lymphoma (MZL), MALT lymphoma, or B-small lymphocytic lymphoma (B-SLL).
- Transfection of BL cells with galectin-3 increased resistance to anti-Fas-induced apoptosis.
- Truncation of galectin-3 in PEL cells increased sensitivity to anti-Fas-induced apoptosis.
- Galectin-3 expression was lowest in germinal center and plasma B cells and highest in naive and memory B cells.
Conclusions:
- Aberrantly increased galectin-3 levels in specific B-cell populations may provide a survival advantage during transformation or progression of certain B-cell neoplasms.
- Galectin-3 expression is a distinguishing feature between certain B-cell lymphoma subtypes.
- Galectin-3 plays a functional role in regulating apoptosis in B cells, impacting lymphomagenesis.