Interaction of acute lymphopblastic leukemia cells with C-type lectins DC-SIGN and L-SIGN.
The C-type lectins DC-SIGN (CD209) and L-SIGN (CD299) recognize defined carbohydrates expressed on pathogens and cells. Those lectins are expressed on dendritic cells (DC) and/or on liver-sinusoidal endothelial cells. Both cell types modulate immune responses. In acute lymphoblastic leukemia (ALL), aberrant glycosylation of blast cells can alter their interaction with the C-type lectins DC-SIGN and L-SIGN, thereby affecting their immunological elimination. We investigated whether recombinant DC-SIGN and L-SIGN bind to blood or bone marrow cells from B- and T-ALL patients and compared that with binding of peripheral blood lymphocytes from healthy donors. It was found that increased binding of ALL cells to DC-SIGN and L-SIGN was observed compared to cells from healthy donors. Furthermore, L-SIGN bound a higher percentage of leukemic and normal cells than DC-SIGN. B-ALL bone marrow cells showed the highest binding to L-SIGN. DC-SIGN bound equally well to B-ALL and T-ALL cells. Within ALL subtypes, DC-SIGN binding was higher with mature T-ALL. Interestingly, our data demonstrate that increased binding of DC-SIGN and L-SIGN to peripheral leukemic cells from B-ALL patients is associated with poor survival. These data demonstrate that high binding of B-ALL peripheral blood cells to DC-SIGN and L-SIGN correlates with poor prognosis. Apparently, when B-ALL cells enter the blood circulation and are able to interact with DC-SIGN and L-SIGN the immune response is shifted toward tolerance. Additional studies are necessary to ascertain the possible role of these results in terms of disease pathogenesis and their potential as target to eradicate leukemic cells.
Gijzen
Karlijn
K
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Raymakers
Reinier A P
RA
Broers
Karin M
KM
Figdor
Carl G
CG
Torensma
Ruurd
R
D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D002051:Burkitt Lymphoma / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D002241:Carbohydrates / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D018572:Disease-Free Survival; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006031:Glycosylation; D006801:Humans; D007108:Immune Tolerance; D037181:Lectins, C-Type / Q000276:immunology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology*; D015996:Survival Rate; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D002241:Carbohydrates; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human