GLYCOPROTEINS IN NORMAL & LEUKEMIC CELL DIFFERENTIATION
GLYCOPROTEINS IN NORMAL & LEUKEMIC CELL DIFFERENTIATION
批准号:
3171646
负责人:
MINORU FUKUDA
金额:
$22.0万
依托单位国家:
美国
项目类别:
财政年份:
1983
资助国家:
美国
项目状态:
已结题
起止时间:
1983-01-01 至 1991-12-31
关键词:
T lymphocyte carbohydrate structure cell cell interaction cell differentiation cell membrane genetic library glycolipids glycoprotein structure glycoproteins human tissue hybridomas laboratory mouse laboratory rabbit leukocyte activation /transformation lymphocytic leukemia membrane activity membrane proteins molecular cloning monoclonal antibody myelogenous leukemia myeloid stem cell neoplasm /cancer classification /staging neoplastic cell neoplastic transformation oligosaccharides protein sequence surface antigens tissue /cell culture
中文摘要
其主要目的是研究人类膜的分化。
白细胞(髓样细胞和淋巴样细胞)和评价细胞表面
碳水化合物和糖蛋白作为肿瘤分化标志物可能是
白血病细胞和正常细胞所共有的,取决于
差异化。主要涉及两个方面:
(1)阐明主要细胞表面白唾液的结构
唾液酸糖蛋白在各种白细胞上表达。我们已经分离出一名
从髓系细胞中提取的主要细胞表面唾液酸糖蛋白,发现这
糖蛋白在多种白细胞中表达,包括
粒细胞/单核细胞、B淋巴系和T淋巴系。在……里面
此外,我们还发现这种糖蛋白是高度糖基化的
由O-连接的低聚糖及其结构
低聚糖对每个细胞谱系和不同的细胞谱系都是特有的
髓系细胞的成熟期。进一步的研究将表现出
白涎素的碳水化合物链,沿着分化途径
不同的细胞谱系,旨在阐明白涎素的可能作用
糖基化。这些研究将得到隔离和
Leukosialin编码的cDNA的鉴定,这将使我们能够
阐明其多肽序列。
(2)细胞表面糖蛋白和糖链的分析
白血病细胞中的糖脂。我们发现聚乳糖胺多聚糖和
慢性粒细胞白血病细胞糖脂表达的独特性
碳水化合物结构,如
NeuNAcAlpha2to3GalBeta1to4(FucAlpha1to3)GlcNAcBeta1to3GalBeta1to4(FucAlpha1t
O3)-GlcNActo,以及
NeuNAcAlpha2to3GalBeta1to4GlcNAcBeta1toGalBeta1to4(FucAlpha1to3)GlcNActo.
这些结构在正常成熟的粒细胞或
急性髓系白血病细胞。进一步的研究将产生
并确定是否有针对这些碳水化合物的单抗
这些碳水化合物可作为CML的标志物。结构分析的几点体会
碳水化合物存在于其他白血病细胞中,特别是B淋巴细胞
白血病的启动目的是为了识别碳水化合物
这些白血病细胞所特有的结构。
英文摘要
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.
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