| Literature DB >> 20671121 |
Xin Liu1, 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 Sayers, Mark Kester, Thomas P Loughran.
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.Entities:
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Year: 2010 PMID： 20671121 PMCID： PMC2993625 DOI： 10.1182/blood-2010-02-271080
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113