Blood Journal
Leading the way in experimental and clinical research in hematology

Galectin-3 binds to CD45 on diffuse large B cell lymphoma cells to regulate susceptibility to cell death

  1. Mary C. Clark1,
  2. Mabel Pang1,
  3. Daniel K. Hsu2,
  4. Fu-Tong Liu2,
  5. Sven de Vos3,
  6. Randy D. Gascoyne4,
  7. Jonathan Said1, and
  8. Linda G. Baum1,*
  1. 1 Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, CA, United States;
  2. 2 Department of Dermatology, School of Medicine, University of California at Davis, Sacramento, CA, United States;
  3. 3 Department of Internal Medicine, UCLA School of Medicine, Los Angeles, CA, United States;
  4. 4 Departments of Pathology and Laboratory Medicine, BC Cancer Agency, Centre for Lymphoid Cancers, Vancouver, BC, Canada
  1. * Corresponding author; email: lbaum{at}


Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma and an aggressive malignancy. Galectin-3 (gal-3), the only anti-apoptotic member of the galectin family, is overexpressed in DLBCL. While gal-3 can localize to intracellular sites, gal-3 is secreted by DLBCL cells and binds back to the cell surface in a carbohydrate-dependent manner. The major counterreceptor for gal-3 on DLBCL cells was identified as the transmembrane tyrosine phosphatase CD45. Removal of cell surface gal-3 from CD45 with the polyvalent glycan inhibitor GCS-100 rendered DLBCL cells susceptible to chemotherapeutic agents. Binding of gal-3 to CD45 modulated tyrosine phosphatase activity; removal of endogenous cell surface gal-3 from CD45 with GCS-100 increased phosphatase activity, while addition of exogenous gal-3 reduced phosphatase activity. Moreover, the increased susceptibility of DLBCL cells to chemotherapeutic agents after removal of gal-3 by GCS-100 required CD45 phosphatase activity. Gal-3 binding to a subset of highly glycosylated CD45 glycoforms was regulated by the C2GnT-1 glycosyltransferase, indicating that specific glycosylation of CD45 is important for regulation of gal-3-mediated signaling. These data identify a novel role for cell surface gal-3 and CD45 in DLBCL survival and suggest novel therapeutic targets to sensitize DLBCL cells to death.

  • Submitted June 20, 2012.
  • Accepted September 23, 2012.