title: Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies.
abstract: Sphingolipids, such as ceramide, sphingosine and sphingosine 1-phosphate (S1P) are bioactive molecules that have important functions in a variety of cellular processes, which include proliferation, survival, differentiation and cellular responses to stress. Sphingolipids have a major impact on the determination of cell fate by contributing to either cell survival or death. Although ceramide and sphingosine are usually considered to induce cell death, S1P promotes survival of cells. Sphingosine kinases (SPHKs) are the enzymes that catalyze the conversion of sphingosine to S1P. There are two isoforms, SPHK1 and SPHK2, which are encoded by different genes. SPHK1 has recently been implicated in contributing to cell transformation, tumor angiogenesis and metastatic spread, as well as cancer cell multidrug-resistance. More recent findings suggest that SPHK2 also has a role in cancer progression. This review is an overview of our understanding of the role of SPHKs and S1P in hematopoietic malignancies and provides information on the current status of SPHK inhibitors with respect to their therapeutic potential in the treatment of hematological cancers.
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Evangelisti
authors.affiliation: Institute of Molecular Genetics, National Research Council-Rizzoli Orthopedic Institute and Muscoloskeletal Cell Biology Laboratory, IOR, Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Evangelisti
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Buontempo
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lonetti
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Orsini
authors.affiliation: Institute of Molecular Genetics, National Research Council-Rizzoli Orthopedic Institute and Muscoloskeletal Cell Biology Laboratory, IOR, Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Chiarini
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: J T
authors.initials: JT
authors.lastname: Barata
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland, UK.
authors.forename: S
authors.initials: S
authors.lastname: Pyne
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Pyne
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Martelli
mesh_terms: D018450:Disease Progression; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D008246:Lysophospholipids / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy / Q000379:methods*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D013110:Sphingosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D000099157:Sphingosine Kinase
chemical_list: D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D047428:Protein Kinase Inhibitors; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate; C000594250:sphingosine kinase 2, human