Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies

C Evangelisti, C Evangelisti, F Buontempo, A Lonetti, E Orsini, F Chiarini, J T Barata, S Pyne, N J Pyne, A M Martelli

Research output: Contribution to journalLiterature review

14 Citations (Scopus)

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 haematological cancers.
LanguageEnglish
Pages2142–2151
Number of pages10
JournalLeukemia
Volume30
Early online date27 Jul 2016
DOIs
Publication statusPublished - 1 Nov 2016

Fingerprint

Hematologic Neoplasms
Sphingosine
Sphingolipids
Ceramides
Neoplasms
Cell Survival
Cell Death
Multiple Drug Resistance
Therapeutics
Protein Isoforms
sphingosine kinase
sphingosine 1-phosphate
Enzymes
Genes

Keywords

  • apoptosis
  • ceramide
  • drug-resistance
  • leukemia
  • lymphoma
  • multiple myeloma
  • sphingosine
  • sphingosine 1-phosphate

Cite this

Evangelisti, C., Evangelisti, C., Buontempo, F., Lonetti, A., Orsini, E., Chiarini, F., ... Martelli, A. M. (2016). Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies. Leukemia, 30, 2142–2151. https://doi.org/10.1038/leu.2016.208
Evangelisti, C ; Evangelisti, C ; Buontempo, F ; Lonetti, A ; Orsini, E ; Chiarini, F ; Barata, J T ; Pyne, S ; Pyne, N J ; Martelli, A M. / Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies. In: Leukemia. 2016 ; Vol. 30. pp. 2142–2151.
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Evangelisti, C, Evangelisti, C, Buontempo, F, Lonetti, A, Orsini, E, Chiarini, F, Barata, JT, Pyne, S, Pyne, NJ & Martelli, AM 2016, 'Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies' Leukemia, vol. 30, pp. 2142–2151. https://doi.org/10.1038/leu.2016.208

Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies. / Evangelisti, C; Evangelisti, C; Buontempo, F; Lonetti, A; Orsini, E; Chiarini, F; Barata, J T; Pyne, S; Pyne, N J; Martelli, A M.

In: Leukemia, Vol. 30, 01.11.2016, p. 2142–2151.

Research output: Contribution to journalLiterature review

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Evangelisti C, Evangelisti C, Buontempo F, Lonetti A, Orsini E, Chiarini F et al. Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies. Leukemia. 2016 Nov 1;30:2142–2151. https://doi.org/10.1038/leu.2016.208