LENALIDOMIDE'IN'COMBINATION'WITH'ARSENIC'TRIOXIDE:'AN'EFFECTIVE'
POSTER'2'
THERAPY'FOR'PRIMARY'EFFUSION'LYMPHOMA'
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Sara! Moodad1,! Rana! El! Hajj2,! Rita! Hleihel1,3,! Layal! Hajjar3,! Nadim! Tawil4,! Martin! Karam4,! Maguy!
Hamieh5,!Raghida!Abou!Merhi6,!Marwan!El!Sabban3!and!Hiba!El!Hajj5!
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(1)Department! of! Internal! Medicine,! Faculty! of! Medicine,! American! University! of! Beirut,! Beirut,!
Lebanon,! (2)Department! of! Pathology! and! Laboratory! Medicine,! Faculty! of! Medicine,! American!
University!of!Beirut,!Beirut,!Lebanon,!(3)Department!of!Anatomy,!Cell!Biology!and!Physiology,!Faculty!
of!Medicine,!American!University!of!Beirut,!Beirut,!Lebanon,!(4)McGill!University,!Montreal,!Canada,!
(5)Department! of! Experimental! Pathology,! Immunology,! and! Microbiology,! Faculty! of! Medicine,!
American! University! of! Beirut,! Beirut,! Lebanon,! (6)Department! of! Biology,! Faculty! of!
Sciences,Lebanese!University,!Beirut,!Lebanon!
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Primary! Effusion! Lymphoma! (PEL)! is! a! rare! aggressive! subset! of! NonJHodgkin! B! cell!
lymphoma.! PEL! is! secondary! to! Kaposi! Sarcoma! Herpes! Virus! (KSHV)! and! predominantly!
develops!in!serous!cavities.!Conventional!chemotherapy!remains!the!treatment!of!choice!of!
PEL! and! yields! high! response! rates! with! no! significant! comorbidities.! Yet,! chemotherapy!
often! fails! in! achieving! or! maintaining! longJterm! remission.! Lenalidomide! (Lena),! an!
immunomodulatory! drug,! displayed! some! efficacy! in! the! treatment! of! PEL.! On! the! other!
hand,!Arsenic!trioxide!(ATO)!in!combination!with!other!agents,!effectively!treated!a!number!
of! blood! malignancies,! including! PEL.! In! this! study,! we! present! evidence! that! the!
combination!of!ATO/Lena!significantly!enhanced!survival!of!PEL!mice,!decreased!the!volume!
of! exacerbated! ascites! in! the! peritoneum,! and! reduced! tumor! infiltration! in! organs! of!
treated! animals.! In!exUvivo!treated! PEL! cells,! ATO/Lena! decreased! the! proliferation! and!
downregulated! the! expression! of! KSHV! latent! viral! proteins.! This! was! associated! with!
decreased!NFJκB!activation,!resulting!in!reactivation!of!viral!replication,!downregulation!of!
interleukinJ6!(ILJ6)!and!ILJ10,!inhibition!of!Vascular!Endothelial!Growth!Factor!and!apoptosis.!
Our! results! elucidate! the! mechanism! of! action! of! ATO/Lena,! and! present! it! as! a! promising!
targeted! therapeutic! modality! in! PEL! management,! which! warrant! further! clinical!
investigation.!
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