MEMBRANE SIALOGLYCOCONJUGATES AND SIALYLTRANSFERASES

我们一直在研究膜糖偶联物的变化，这可能 与慢性粒细胞白血病(CML)的发病机制有关。我们 最近报道，慢性粒细胞白血病细胞表现出明显的活性增强 O-连接半乳糖β-1，3-半乳糖的2，3-唾液酸基转移酶 受体，并发现了特定CML超唾液酸化的证据 细胞膜糖蛋白。 我们的具体目标是： 1.确定异常受体特异性唾液酸基转移酶 O-连接膜糖蛋白的活性和超唾液酸化是独一无二的 到Phi阳性的慢性粒细胞白血病。 2.异常Gal-β1，3-GalNAc-About的分离和鉴定 CML和正常白细胞的2，3-唾液酸基转移酶 它的活性被改变的蛋白催化的磷酸化所刺激。 癌基因产物c-abl P210。 3.确定CML细胞结合位点的超唾液酸化是否对 调节骨髓生成的因子有助于增殖性 慢性粒细胞白血病在骨髓中相对于正常粒细胞前体的优势。 4.探索抑制合成的化疗药物或 膜唾液酸的表达也可能逆转高唾液酸化 和慢性粒细胞白血病细胞的异常功能，从而有助于临床 治疗。 这些研究可以提供有关病理生理学的重要信息。 骨髓增殖性疾病，并可能开启新的治疗方法 CML更好的生理控制的可能性。

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.