ABERRANT GLYCOSYLATION OF L-SELECTIN ON THE LYMPHOCYTES OF CHRONIC LYMPHOCYTIC-LEUKEMIA

Abnormal trafficking of chronic lymphocytic leukemia (CLL) cells may a ccount for the differences in accumulation of malignant lymphocytes wi thin the bone marrow and lymphoid tissues of this lymphoproliferative disorder. We therefore hypothesized that CLL cells aberrantly express one or more receptors involved in lymphocyte trafficking. Leukemia cel ls from patients with B-cell CLL showed no quantitative difference in surface expression of L-selectin, LFA-1, or CD44 by flow cytometry com pared to normal B cells. Analysis of L-selectin by dodecyl sulfate/pol yacrylamide gel electrophoresis (SDS-PAGE) and Western blot, however, demonstrated a consistent, reproducible approximately 3.7 kDa decrease in the M(r) of L-selectin on CLL cells compared to normal 8 cells. In contrast, Western blot analysis revealed no obvious qualitative abnor mality in either CD11a (the alpha-chain of LFA-1) or CD44 on CLL cells . Analysis of L-selectin cDNA by polymerase chain reaction revealed id entically sized products for both normal and CLL cells, suggesting tha t the abnormality in M(r) does not result from a difference in primary structure. Inhibition of N-linked glycosylation by tunicamycin result ed in the production of identical-sized nascent L-selectin by normal a nd CLL cells. These studies demonstrate that L-selectin on CLL cells i s aberrantly glycosylated compared to normal peripheral blood lymphocy tes. The functional importance of this aberrant glycosylation is uncle ar, however, sinCe L-Selectin is shed normally from phorbol myristate acetate (PMA)-stimulated CLL cells and since normal and CLL lymphocyte s bind equally well in vitro to high endothelial venules. Understandin g the mechanism that accounts for the aberrance may provide important insights into the molecular basis of CLL.