Targeting of survivin by nanoliposomal ceramide induces complete remission in a rat model of NK-LGL leukemia

Xin Liu, Lindsay Ryland, Jun Yang, Aijun Liao, Cesar Aliaga, Rebecca Watts, Su Fern Tan, James Kaiser, Sriram S. Shanmugavelandy, Andrew Rogers, Kathleen Loughran, Bailey Petersen, Jonathan Yuen, Fanxue Meng, Kendall Thomas Baab, Nancy Ruth Jarbadan, Kathleen Broeg, Ranran Zhang, Jason Liao, Thomas Joseph SayersMark Kester, Thomas P. Loughran

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

The natural killer (NK) type of aggressive large granular lymphocytic (LGL) leukemia is a fatal illness that pursues a rapid clinical course. There are no effective therapies for this illness, and pathogenetic mechanisms remain undefined. Here we report that the survivin was highly expressed in both aggressive and chronic leukemic NK cells but not in normal NK cells. In vitro treatment of human and rat NK-LGL leukemia cells with cell-permeable, short-chain C6-ceramide (C6) in nanoliposomal formulation led to caspase-dependent apoptosis and diminished survivin protein expression, in a time- and dose-dependent manner. Importantly, systemic intravenous delivery of nanoliposomal ceramide induced complete remission in the syngeneic Fischer F344 rat model of aggressive NK-LGL leukemia. Therapeutic efficacy was associated with decreased expression of survivin in vivo. These data suggest that in vivo targeting of survivin through delivery of nanoliposomal C6-ceramide may be a promising therapeutic approach for a fatal leukemia.

Original languageEnglish (US)
Pages (from-to)4192-4201
Number of pages10
JournalBlood
Volume116
Issue number20
DOIs
StatePublished - Nov 18 2010

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Liu, X., Ryland, L., Yang, J., Liao, A., Aliaga, C., Watts, R., Tan, S. F., Kaiser, J., Shanmugavelandy, S. S., Rogers, A., Loughran, K., Petersen, B., Yuen, J., Meng, F., Baab, K. T., Jarbadan, N. R., Broeg, K., Zhang, R., Liao, J., ... Loughran, T. P. (2010). Targeting of survivin by nanoliposomal ceramide induces complete remission in a rat model of NK-LGL leukemia. Blood, 116(20), 4192-4201. https://doi.org/10.1182/blood-2010-02-271080