Sphingolipid players in the leukemia arena.
Sphingolipids function as bioactive mediators of different cellular processes, mostly proliferation, survival, differentiation and apoptosis, besides being structural components of cellular membranes. Involvement of sphingolipid metabolism in cancerogenesis was demonstrated in solid tumors as well as in hematological malignancies. Herein, we describe the main biological and clinical aspects of leukemias and summarize data regarding sphingolipids as mediators of apoptosis triggered in response to anti-leukemic agents and synthetic analogs as inducers of cell death as well. We also report the contribution of molecules that modulate sphingolipid metabolism to development of encouraging strategies for leukemia treatment. Finally we address how deregulation of sphingolipid metabolism is associated to occurrence of therapy resistance both in vitro and in vivo. Sphingolipids can be considered promising therapeutic tools alone or in combination with other compounds, as well as valid targets in the attempt to eradicate leukemia and overcome drug resistance.
Ricci
Clara
C
Laboratory of Biochemistry and Molecular Biology, San Paolo University Hospital, Medical School, University of Milan, 20142 via A. di Rudinì, 8-Milan, Italy.
Onida
Francesco
F
Ghidoni
Riccardo
R
D000970:Antineoplastic Agents / Q000627:therapeutic use; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000503:physiopathology*; D013107:Sphingolipids / Q000502:physiology*
D000970:Antineoplastic Agents; D013107:Sphingolipids