SPHK1 and primary effusion lymphoma: On a different note, blocking SPHK pathways, particularly via SPHK2, is cytotoxic to murine models of primary effusion lymphoma (PEL), a human herpesvirus 8-related neoplasm, due to the upregulation of ceramide synthase and subsequent accumulation of cytotoxic ceramide species that lead to apoptosis by viral lytic gene expression [146,147].