TY - JOUR
T1 - Targeting of survivin by nanoliposomal ceramide induces complete remission in a rat model of NK-LGL leukemia
AU - Liu, Xin
AU - Ryland, Lindsay
AU - Yang, Jun
AU - Liao, Aijun
AU - Aliaga, Cesar
AU - Watts, Rebecca
AU - Tan, Su Fern
AU - Kaiser, James
AU - Shanmugavelandy, Sriram S.
AU - Rogers, Andrew
AU - Loughran, Kathleen
AU - Petersen, Bailey
AU - Yuen, Jonathan
AU - Meng, Fanxue
AU - Baab, Kendall Thomas
AU - Jarbadan, Nancy Ruth
AU - Broeg, Kathleen
AU - Zhang, Ranran
AU - Liao, Jason
AU - Sayers, Thomas Joseph
AU - Kester, Mark
AU - Loughran, Thomas P.
PY - 2010/11/18
Y1 - 2010/11/18
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=78549233741&partnerID=8YFLogxK
U2 - 10.1182/blood-2010-02-271080
DO - 10.1182/blood-2010-02-271080
M3 - Article
C2 - 20671121
AN - SCOPUS:78549233741
SN - 0006-4971
VL - 116
SP - 4192
EP - 4201
JO - Blood
JF - Blood
IS - 20
ER -