HUMAN T-CELL LEUKEMIA VIRUS-1 ENCODED TAX PROTEIN TRANSACTIVATES ALPHA-1-]3 FUCOSYL-TRANSFERASE FUC-T-VII, WHICH SYNTHESIZES SIALYL-LEWIS-X, A SERECTIN LIGAND EXPRESSED ON ADULT T-CELL LEUKEMIA-CELLS

Leukemia cells in patients with adult T-cell leukemia (ATL) and relate d cell lines strongly express the carbohydrate determinant sialyl Lewi s X, a ligand for selectins, Its expression is thought to be related c losely to the extravascular infiltration of the leukemia cells, Human T-cell leukemia virus type 1 (HTLV-1), the etiological agent of ATL, p roduces Tax protein, which is implicated in leukemogenesis through its transactivating effect on various cellular genes, In this study we in vestigated the transactivating effect of HTLV-1 Tax on the alpha 1-->3 fucosyltransferase Fuc-T VII, the putative rate-limiting enzyme in th e synthesis of sialyl Lewis X in human leukocytes using JPX-9 cells, J PX-9 is a subclone of a non-ATL human lymphocytic leukemia cell line, Jurkat, and was established by introducing a metallothionein promoter- driven Tax expression plasmid, The JPX-9 cells as well as parental Jur kat cells did not express Fuc-T VII mRNA under normal culture conditio ns, When cultured in the presence of 10 mu M CdCl2, Tax was induced an d a significant amount of the Fuc-T VII message was ascertained by Nor thern blotting, The amount of the message was 24.5 times as much as wa s detected in non-treated cells, and was comparable to that which appe ared by TPA stimulation of the cells, which is supposed to simulate th e sequence of events occurring in normal activation of T lymphocytes a ctivated by more physiological stimuli, Sialyl Lewis X determinant was expressed at the surface of CdCl2-treated cells, while the determinan t was not detectable on either unstimulated JPX-9 or parental Jurkat c ells, These results indicate that expression of sialyl Lewis X on leuk emic cells in patients with ATL is at least partly due to the transact ivation of the Fuc-T VII gene induced by the HTLV-1 Tax, and suggest t hat this leads to the accelerated extravascular infiltration of ATL ce lls, (C) 1997 Academic Press.