MEMBRANE SIALOGLYCOCONJUGATES AND SIALYLTRANSFERASES IN

膜唾液酸糖缀合物和唾液酸转移酶

• 批准号: 3169848
• 负责人: Robert N. Taub
• 金额: $ 24.44万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-06-01 至 1988-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3169848
• 关键词: affinity chromatography; alkylating agents; antineoplastic antibiotics; blood drug; bone marrow; busulfan; cell adhesion; chemical conjugate; cytosine arabinoside; doxorubicin; electrofocusing; enzyme induction /repression; exo alpha sialidase; granulocyte; hematopoietic stem cells; histochemistry /cytochemistry; human tissue; immunochemistry; immunofluorescence technique; lactoferrin; leukopoiesis; membrane activity; monocyte; myelogenous leukemia; neoplasm /cancer chemotherapy; neutrophil; oligosaccharides; oncogenes; phosphorylation; radiotracer; sialate; tissue /cell culture; transferase

We have been investigating alterations in membrane glycoconjugates that may be related to the pathogenesis of chronic myelogenous leukemia (CML). We recently reported that CML cells show increased activity of a distinct about 2,3-sialyltransferase specific for O-linked Gal-Beta1,3-GalNAc acceptors and have also found evidence for hypersialylation of specific CML cell membrane glycoproteins. Our specific aims are: 1. To determine if the abnormal acceptor-specific sialyltransferase activity and hypersialylation of O-linked membrane glycoproteins are unique to PhI-positive CML. 2. To isolate and characterize the aberrant Gal-Beta 1,3-GalNAc-about 2,3-sialyltransferase from CML and normal leukocytes and determine whether its activity is stimulated by phosphorylation catalyzed by the altered oncogene product c-abl P210. 3. To determine whether hypersialylation of CML cell binding sites for factors that regulate myelopoiesis contributes to the proliferative advantage of CML versus normal granulocyte precursors in the bone marrow. 4. To explore whether chemotherapeutic agents that inhibit the synthesis or expression of membrane sialic acid may also reverse the hypersialylation and abnormal functioning of CML cells and thereby contribute to clinical treatment. These studies could yield important information about the pathophysiology of the myeloproliferative diseases, and could open new therapeutic possibilities for the better physiologic control of CML.

我们一直在研究膜糖复合物的改变， 与慢性粒细胞白血病（CML）的发病机制有关。 我们 最近报道，CML细胞显示出一种独特的 对O-连接的Gal-Beta1，3-GalNAc特异的约2，3-唾液酸转移酶 并发现了特定CML的高唾液酸化的证据 细胞膜糖蛋白 我们的具体目标是： 1.确定异常的受体特异性唾液酸转移酶 O-连接的膜糖蛋白的活性和过度唾液酸化是独特的 转化为Ph阳性CML 2.为了分离和表征异常的Gal-Beta 1，3-GalNAc-约 2，3-唾液酸转移酶，并确定是否 它的活性是由改变的 癌基因产物c-abl P210。 3.为了确定CML细胞结合位点的唾液酸化是否 调节骨髓生成的因子有助于骨髓增生异常综合征的发生。 骨髓中CML相对于正常粒细胞前体的优势。 4.为了探索是否化疗药物抑制合成或 膜唾液酸的表达也可以逆转高唾液酸化 和CML细胞的异常功能，从而有助于临床 治疗 这些研究可以产生关于病理生理学的重要信息， 骨髓增生性疾病，并可能开辟新的治疗方法 更好的生理控制CML的可能性。