Expression of functionally glycosylated PSGL-1 in ALK-positive anaplastic large cell lymphoma

Abstract

Anaplastic lymphoma kinase (ALK)-positive (ALK+) anaplastic large cell lymphoma (ALCL) is defined as a CD30-positive mature T-cell lymphoma characterized by proliferation of large anaplastic cells and aberrant ALK protein expression. These cells often infiltrate lymphatic sinuses, proliferate and exhibit intercellular cohesiveness and accumulate around blood vessels. However, molecular mechanisms underlying such vascular-related histogenesis remain to be elucidated. Since PSGL-1 is more highly expressed in ALK+ ALCL than in other T-cell lymphomas and sLe^x glycan expression has been reported in ALK+ ALCL, the interaction between PSGL-1, which is functionally glycosylated with sLe^x, and P-selectin, which is expressed on endothelial cells, may contribute to such vascular-related histogenesis. To analyze glycans on PSGL-1 expressed in ALK+ ALCL in the context of P-selectin binding function, we first performed immunohistochemical analysis of 12 cases of ALK+ ALCL to identify those that express both PSGL-1 and sLe^x glycans and found that a substantial portion of both molecules co-localizes in those cases. We then conducted western blot analysis, together with glycosyltransferase gene expression analysis, of ALK+ ALCL cells and observed that PSGL-1 is decorated with sLe^x glycans, especially those displayed on core 2 O-glycans. Finally, we carried out a P-selectin•IgM chimera binding assay to show that ALK+ ALCL cells bind to P-selectin. These results indicate that the PSGL-1 glycoform expressed on ALK+ ALCL cells is functional and that interaction of functionally glycosylated PSGL-1 with P-selectin may be partially responsible for the vascular-related histogenesis characteristics of ALK+ ALCL.

Keywords: Anaplastic large cell lymphoma (ALCL); Anaplastic lymphoma kinase (ALK); Glycosylation; P-selectin; P-selectin glycoprotein ligand 1 (PSGL-1); Sialyl Lewis x (sLe(x)).