An Anti-Apoptotic Role for Galectin-3 in Diffuse Large B-Cell Lymphomas

Katrina K. Hoyer, Mabel Pang, Dorina Gui, I. Peter Shintaku, Ichiro Kuwabara, Fu-Tong Liu, Jonathan W. Said, Linda G. Baum, Michael A. Teitell

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

Increased resistance to apoptosis promotes lymphomagenesis with aberrant expression of cell survival proteins such as BCL-2 and c-MYC occurring in distinct lymphoma subtypes. Galectin-3 is an anti-apoptotic protein that protects T cells, macrophages, and breast carcinoma cells from death triggered by a variety of agents. We have found high levels of galectin-3 protein expression in a subset of B-cell neoplasms including diffuse large B-cell lymphoma (DL-BCL), primary effusion lymphoma (PEL), and multiple myeloma (MM), in both cell lines and patient samples. However, we failed to detect galectin-3 in Burkitt lymphoma (BL), follicular lymphoma (FL), marginal zone lymphoma (MZL), MALT lymphoma or B-small lymphocytic lymphoma (B-SLL) cell lines or patient samples. To determine whether galectin-3 expression protects B cells from apoptosis, galectin-3-negative BL cells were transfected with a galectin-3 expressing plasmid, which resulted in markedly increased resistance to anti-Fas-induced cell death. In contrast, galectin-3-positive PEL cells transfected with an amino-terminal truncated galectin-3 vector showed increased sensitivity to anti-Fas induced apoptosis. During normal B-cell development, galectin-3 expression was lowest in germinal center and plasma B cells, from which DLBCL, PEL, and MM derive, and highest in long-lived naïve and memory B cells. This pattern of expression suggests that aberrantly increased galectin-3 levels in specific B-cell populations may yield a protective advantage during transformation and/or progression of certain B-cell neoplasms.

Original languageEnglish (US)
Pages (from-to)893-902
Number of pages10
JournalAmerican Journal of Pathology
Volume164
Issue number3
StatePublished - Mar 2004

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Hoyer, K. K., Pang, M., Gui, D., Shintaku, I. P., Kuwabara, I., Liu, F-T., Said, J. W., Baum, L. G., & Teitell, M. A. (2004). An Anti-Apoptotic Role for Galectin-3 in Diffuse Large B-Cell Lymphomas. American Journal of Pathology, 164(3), 893-902.