Drug Resistance in Chronic Myelogenous Leukemia Caused by Sphingosine Kinases

Sphingosine 1-Phosphate (S1P) is a mitogenic lipid molecule formed by the enzymes, Sphingosine Kinase (SphK) 1 and 2. SphK1, which is commonly over expressed in malignant tumours, is recognized as a significant contributor to cancer cell survival and tumour angiogenesis, and is accordingly implicated in the pathogenesis of various types of cancer. Initial studies focused on nonhaemopoietic malignancies; however a growing body of literature on the role of sphingolipid metabolism in haemopoietic malignancies is now emerging. In particular, Sphk1 is implicated in the resistance of Tyrosin Kinase Inihibitors (TKIs) in Chronic Myelogenous Leukemia (CML) Here, we discuss the roles of the SphKs in CML and the compounds currently available in order to develop new combinatorial therapeutic approaches.