Alpha-2,6-sialylation regulation in CD34+ progenitor cells in the human bone marrow and granulocyte colony-stimulating factor mobilization.

Abstract

The use of peripheral blood (PB) progenitor cells to reconstitute hematopoiesis after high-dose chemotherapy is now common practice in the treatment of malignancies. Growth factors such as granulocyte colony-stimulating factor (G-CSF) induce high proliferation and self-renewal within the stem cell compartment of the bone marrow. This is followed by the release of a very high number of progenitor cells into the peripheral blood, the mechanism of which remains unclear. Previously, we have showed that high cell-surface sialylation reduces matured myeloid attachment to the bone marrow stroma, which is likely to help their release into the peripheral blood. Consequently, we decided to investigate the possibility that sialylation may also contribute to the CD34(+) cell release into the peripheral blood during G-CSF treatment. We found that G-CSF-mobilized PB CD34(+) cells exhibit an increase in the sialyltransferase ST6Gal-I mRNA level. The analysis of the heterogeneity of ST6Gal-I transcripts showed a predominance of the Y form in both bone marrow (BM) and G-CSF PB CD34(+) cells. Higher levels in ST6Gal-I mRNA resulted in a higher expression of alpha-2,6-sialylation on the surface of G-CSF PB CD34(+) cells when compared to noninduced PB CD34(+) cells but not higher to BM CD34(+) cells. Our present results, together with recent observations, suggest that ST6Gal-I and alpha-2,6-sialylation expression in myeloid cells is tightly dependent on the presence of G-CSF in their environment. Up-regulation of ST6Gal-I together with alpha-2,6-sialylation of cell surface glycoproteins is likely to modulate cellular adherence and survival of progenitor cells.