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B-Cell Leukemia

Transfection of antisense core 2 β1,6-N-acetylglucosaminyltransferase-1 cDNA suppresses selectin ligand expression and tissue infiltration of B-cell precursor leukemia cells

Abstract

B-cell precursor (BCP) leukemia cells infiltrate into peripheral organs and the disease often relapses. Inhibition of tissue infiltration may improve the treatment outcome of BCP-leukemia patients. Selectin ligand has been suggested to play an important role in the infiltration of leukemia cells. However, the regulation mechanisms and involvement in tissue infiltration of selectin ligand expression in BCP-leukemia cells are not fully understood. In this study, we report that BCP-leukemia cells express selectin ligand on O-sialoglycoproteins. Core 2 β1,6-N-acetylglucosaminyltransferase-1 (C2GnT-1) is mainly expressed in BCP-leukemia cells. Transfection of the antisense C2GnT-1 cDNA resulted in a significant reduction of either selectin ligand expression or selectin-dependent cell adhesion in BCP-leukemia cell line KM3 cells. Migration ability into mouse peripheral organs was reduced significantly in the antisense transfectant. These findings suggest that C2GnT-1 regulates selectin ligand expression. Downregulation of the selectin ligand expression level inhibits tissue infiltration of BCP-leukemia cells. C2GnT-1 may be a candidate of therapeutic target for the inhibition of infiltration of leukemia cells.

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Acknowledgements

We thank Taeko Inageta, Yumi Nakamichi, Kazunori Nakamura, and Hiroyuki Matsumaru for their technical support and Tomomi Yaguchi for her secretarial assistance. This work was supported in part by Core Research for Evolution Science and Technology (CREST) of Japan Science and Technology Corporation. This work was also supported in part by a Grant-in-Aid for Scientific Research on Priority Areas No. 12033215 and a Grant for General Scientific Research No. 11670147 from MEXT Japan (to MN), and by the Japan Leukemia Research Fund (to MN). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked ‘advertisement’ in accordance with 18 USC Section 1734 solely to indicate this fact.

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Correspondence to M Nakamura.

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Kikuchi, J., Ozaki, H., Nonomura, C. et al. Transfection of antisense core 2 β1,6-N-acetylglucosaminyltransferase-1 cDNA suppresses selectin ligand expression and tissue infiltration of B-cell precursor leukemia cells. Leukemia 19, 1934–1940 (2005). https://doi.org/10.1038/sj.leu.2403951

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