title: Oncogenic properties of sphingosine kinases in haematological malignancies.
abstract: The sphingosine kinases (SphKs) have relatively recently been implicated in contributing to malignant cellular processes with particular interest in the oncogenic properties of SPHK1. Whilst SPHK1 has received considerable attention as a putative oncoprotein, SPHK2 has been much more difficult to study, with often conflicting data surrounding its role in cancer. Initial studies focused on non-haemopoietic malignancies, however a growing body of literature on the role of sphingolipid metabolism in haemopoietic malignancies is now emerging. This review provides an overview of the current state of knowledge of the SphKs and the bioactive lipid sphingosine 1-phosphate (S1P), the product of the reaction they catalyse. It then reviews the current literature regarding the roles of S1P and the SphKs in haemopoietic malignancies and discusses the compounds currently available that modulate sphingolipid metabolism and their potential and shortcomings as therapeutic agents for the treatment of haematological malignancies.
authors.affiliation: Westmead Institute for Cancer Research, Westmead Millennium Institute, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Craig T
authors.initials: CT
authors.lastname: Wallington-Beddoe
authors.affiliation: Haematology Department, Westmead Hospital, Westmead, NSW, Australia.
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bradstock
authors.affiliation: Westmead Institute for Cancer Research, Westmead Millennium Institute, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Bendall
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D000099157:Sphingosine Kinase
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate