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Blood, 1 March 2007, Vol. 109, No. 5, pp. 2165-2173.
Prepublished online as a Blood First Edition Paper on November 2, 2006; DOI 10.1182/blood-2006-06-028092.
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NEOPLASIA
Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling
Sang-Hoon Sin1,2,
Debasmita Roy1,2,
Ling Wang1,2,
Michelle R. Staudt1,2,
Farnaz D. Fakhari1,2,
Dhavalkumar D. Patel1,4,
David Henry5,6,
William J. Harrington, Jr7,8,
Blossom A. Damania1,2, and
Dirk P. Dittmer1,2
1 Department of Microbiology and Immunology, University of North Carolina at Chapel Hill;
2 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill;
3 Department of Medicine, University of North Carolina at Chapel Hill;
4 Thurston Arthritis Research Center, University of North Carolina at Chapel Hill;
5 Department of Medicine, University of Pennsylvania, Philadelphia;
6 Joan Karnell Cancer Center, University of Pennsylvania, Philadelphia;
7 Sylvester Cancer Center, University of Miami, FL;
8 Department of Medicine, University of Miami, FL
The antitumor potency of the mTOR inhibitor rapamycin (sirolimus) is the subject of intense investigations. Primary effusion lymphoma (PEL) appears as an AIDS-defining lymphoma and like Kaposi sarcoma has been linked to Kaposi sarcomaassociated herpesvirus (KSHV). We find that (1) rapamycin is efficacious against PEL in culture and in a murine xenograft model; (2) mTOR, its activator Akt, and its target p70S6 kinase are phosphorylated in PEL; (3) rapamycin inhibits mTOR signaling as determined by S6 phosphorylation; (4) KSHV transcription is unaffected; (5) inhibition of IL-10 signaling correlates with drug sensitivity; and (6) addition of exogenous IL-10 or IL-6 can reverse the rapamycin growth arrest. This validates sirolimus as a new treatment option for PEL.

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