The primary objective is to study the differentiation of membranes in human leukocytes (myeloid and lymphoid cells) and to evaluate cell surface carbohydrates and glycoproteins as onco-differentiation markers that may be shared by both leukemic cells and normal cells, depending on the stage of differentiation. Two major aspects deal with: (1) Elucidation of the structure of leukosialin, a major cell surface sialoglycoprotein expressed on various leukocytes. We have isolated a major cell surface sialoglycoprotein from myeloid cells and found that this glycoprotein is expressed in various leukocytes including granulocyte/monocyte, B-lymphoid and T-lymphoid cell lineages. In addition, we have discovered that this glycoprotein is heavily glycosylated by 0-linked oligosaccharides and the structures of those 0-linked oligosaccharides are characteristic to each cell lineage and to different maturation stages of myeloid cells. Further studies will characterize carbohydrate chains of leukosialin, along the differentiation pathways in various cell lineages, aiming at elucidating possible roles of leukosialin glycosylation. These studies will be complemented by isolation and characterization of cDNA coding for Leukosialin, which will enable us to elucidate its peptide sequence. (2) Analysis of the carbohydrate chains of cell surface glycoproteins and glycolipids in leukemic cells. We found that polylactosaminoglycans and glycolipids of chronic myelogenous leukemia (CML) cells express unique carbohydrate structures, such as NeuNAcAlpha2to3GalBeta1to4(FucAlpha1to3)GlcNAcBeta1to3GalBeta1to4(FucAlpha1t o3)-GlcNActo, and NeuNAcAlpha2to3GalBeta1to4GlcNAcBeta1toGalBeta1to4(FucAlpha1to3)GlcNActo. These structures are apparently absent in normal mature granulocytes or acute myelogenous leukemia cells. Further studies will be to generate monoclonal antibodies specific to these carbohydrates and determine if these carbohydrates can be used as CML markers. The structural analysis on carbohydrates present in other leukemic cells, particularly B-,lymphocytic leukemia will be initiated with the aim of identifying carbohydrate structures unique to these leukemic cells.