Vogler W R
Emory University, Department of Medicine, Atlanta, GA 30322.
Leuk Lymphoma. 1994 Mar;13(1-2):53-60. doi: 10.3109/10428199409051652.
The alkyl-lysophospholipids are a new family of anticancer drugs which target the cell membrane as their site of action. Enzymes involved in signal transduction (protein kinase C and phosphatidylinositol phospholipase C), phospholipid biosynthesis (lysophosphatidyl acyltransferase and CTP:cholinephosphate cytidylyltransferase) and maintenance of membrane integrity (Na,K ATPase sodium pump) are inhibited. A unique feature of the alkyl-lysophospholipids is their selective cytotoxicity to neoplastic cells. This suggests that the compound would be an excellent agent for purging residual leukemic cells from marrows of patients in remission prior to autologous bone marrow transplantation. Preclinical studies in a murine leukemia model and in an in vitro human system demonstrated successful elimination of leukemic cells from a mixture of normal and leukemic marrows. Twenty-nine poor risk patients with acute leukemia underwent autologous bone marrow transplantation and were reinfused with marrow treated in vitro with edelfosine. Nine of these patients remain in remission free of leukemia from 368 to 1369 days. These encouraging results warrant further investigation.
烷基溶血磷脂是一类新型抗癌药物，其作用靶点为细胞膜。参与信号转导的酶（蛋白激酶C和磷脂酰肌醇磷脂酶C）、磷脂生物合成（溶血磷脂酰酰基转移酶和CTP：胆碱磷酸胞苷转移酶）以及维持膜完整性的酶（钠钾ATP酶钠泵）均受到抑制。烷基溶血磷脂的一个独特特性是它们对肿瘤细胞具有选择性细胞毒性。这表明该化合物将是在自体骨髓移植前清除缓解期患者骨髓中残留白血病细胞的极佳药物。在小鼠白血病模型和体外人体系统中进行的临床前研究表明，能够成功从正常骨髓和白血病骨髓的混合物中清除白血病细胞。29例急性白血病高危患者接受了自体骨髓移植，并回输了经依地福新体外处理的骨髓。其中9例患者在368至1369天内保持无白血病缓解状态。这些令人鼓舞的结果值得进一步研究。
