Sphingosine kinase 1 protein and mRNA are overexpressed in non-Hodgkin lymphomas and are attractive targets for novel pharmacological interventions

Michael Bayerl, Richard D. Bruggeman, Elizabeth J. Conroy, Jeremy Hengst, Tonya King, Marcela Jimenez, David Claxton, Jong Yun

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Sphingosine kinase 1 (SphK1) is an oncoprotein capable of directly transforming cells and is associated with resistance to chemotherapy and radiotherapy. SphK1 is increased in various human cancers; whereas, blockade restores sensitivity to therapeutic killing in chemotherapy resistant cancer cell lines. We investigated SphK1 expression in clinical tissue samples from patients with non-Hodgkin lymphomas (NHL). Tissues from 69 patients with either NHL (n = 44) or reactive lymphoid hyperplasias (RH) (n = 25) were examined for expression of SphK1 protein by Western blot and immunohistochemistry (IHC), and SphK1 and SphK2 mRNA by quantitative real-time reverse transcriptase polymerase chain reaction. SphK1 protein (p = 0.008) and mRNA (p = 0.035) levels were higher in NHL than RH, with a clear trend toward increasing levels with increasing clinical grade (p = 0.005 for SphK1 protein, p = 0.035 for IHC score and p = 0.002 for SphK1 mRNA). IHC generally confirmed protein signal in neoplastic cells, but some lymphomas exhibited staining in non-neoplastic cells. SphK1 is overexpressed in NHL and increases with increasing clinical grade. These results, combined with prior mechanistic studies suggest that SphK1 is an attractive novel target for pharmacological interventions for NHL.

Original languageEnglish (US)
Pages (from-to)948-954
Number of pages7
JournalLeukemia and Lymphoma
Volume49
Issue number5
DOIs
StatePublished - May 1 2008

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

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