The biology of E-selectin ligands in leukemogenesis

Both the cascade whereby a blood-borne cell enters a tissue and the anchoring of hematopoietic stem/progenitor cells (HSPCs) within bone marrow critically pivots on cell-cell interactions mediated by E-selectin binding to its canonical carbohydrate ligand, the tetrasaccharide termed "sialylated Lewis X" (sLeX). E-selectin, a member of the selectin class of adhesion molecules that is exclusively expressed by vascular endothelium, engages sLeX-bearing glycoconjugates that adorn mature leukocytes and HSPCs, as well as malignant cells, thereby permitting these cells to extravasate into various tissues. E-selectin expression is induced on microvascular endothelial cells within inflammatory loci at all tissues. However, conspicuously, E-selectin is constitutively expressed within microvessels in skin and marrow and, additionally, is inducibly expressed at these sites. Within the marrow, E-selectin receptor/ligand interactions promote lodgment of HSPCs and their malignant counterparts within hematopoietic growth-promoting microenvironments, collectively known as "vascular niches". Indeed, E-selectin receptor/ligand interactions have been reported to regulate both hematopoietic stem, and leukemic, cell proliferative dynamics. As such, signaling induced via engagement of E-selectin ligands is gaining interest as a critical mediator of homeostatic and malignant hematopoiesis, and this review will present current perspectives on the glycoconjugates mediating E-selectin receptor/ligand interactions and their currently defined role(s) in leukemogenesis.