中文摘要：

1-磷酸鞘氨醇（S1P）是重要的磷脂代谢产物并介导广泛的生物学效应,包括细胞增殖、存活和迁移等。S1P在细胞内由鞘氨醇激酶（SphK）使鞘氨醇磷酸化而形成。S1P代谢的异常调节已经成为血液肿瘤发生发展的重要环节。利用抑制剂、激动剂及抗体等靶向SphK-S1P信号通路（包括S1P受体及参与合成和降解的关键酶）已经成为血液肿瘤的新治疗策略。本文综述了SphK-S1P的重要生理作用,重点阐述了其异常调节机制及其靶向治疗在血液肿瘤中病理生理过程中的重要性。首先对磷脂代谢和信号调控进行了概述,然后总结了S1P的合成、代谢、病理和生理作用、异常调节机制以及在血液肿瘤中靶向策略。另外,还讨论了靶向SphK信号通路在新药研发中的前景和重要性。

英文摘要：

Sphingosine 1-phosphate（ S1P） is a bioactive sphingolipid metabolite that mediates diverse cellular processes including proliferation,survival and migration.S1 P is produced from sphingosine by sphingosine kinases（ SphK）. The deregulation of S1 P metabolism has become the major event in cancer progress including hematopoietic malignancy. Targeting SphK-S1 P pathway molecules,including S1 P receptors and the enzymes involved in S1 P biosynthesis or degradation with inhibitors,agonists and antibodies represents novel treatment strategies for hematopoietic malignancy. In this review,we highlight the importance of SphK-S1 P signaling,especially its deregulation mechanisms and targeting strategies in hematopoietic malignancy. After a brief general description of sphingolipid metabolism and signaling,we summarize the biosynthesisand metabolism,physiological and pathological roles,deregulated mechanisms and targeting strategies of SphK-S1 P pathways in hematopoietic malignancy. The potential and prospect of targeting S1 P metabolism and signaling in the development of novel drugs are also discussed.