The overall objective of this research is to understand the course of membrane differentiation in human myeloid (granulocyte-monocyte) cells and to compare membrane differentiation of normal cells with that of leukemic cells by using surface glycoproteins as onco-differentiation markers. Two major aspects deal with: (1) Characterization of membrane glycoproteins expressed on leukemic cells and normal cells at various stages of differentiation and maturation. We have found that distinctly different sets of cell-surface glycoproteins are expressed in leukemic cell lines representing early and late stages of myeloid cell maturation. In addition, some of these glycoproteins appear to be specific to myeloid cells. Studies are in progress to isolate and characterize myeloid-specific glycoproteins (gp130). Further aims are to prepare antibodies specific to such glycoproteins and analyze membrane differentiation in normal and leukemic conditions. Preliminary results indicate that the difference in glycosylation critically influence the apparent molecular weights of gp130. Further studies are to clarify these changes by structural studies. (2) Characterization of the changes in the carbohydrate structures of cell surface glycoproteins during the process of differentiation of normal and leukemic cells with special reference to lactosaminoglycan. We have found that mature granulocytes express a significant amount of lactosaminoglycan which has a structure of Gal-beta-1 to 4(Fuc-alpha-1 to 3) GlcNAc-beta-1 to 3. In addition, mature granulocytes contain a significant amount of sialylated lactosaminoglycan, which contains sialylated fucosyl lactosamine structures in a small quantity. Structural studies will be performed on carbohydrate chains of cell-surface glycoproteins of various myeloid leukemic cells representing different stages of maturation. (M)
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