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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 sarcoma–associated 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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