Lenalidomide in Combination with Arsenic Trioxide: an Effective Therapy for Primary Effusion Lymphoma

Moodad, Sara; El Hajj, Rana; Hleihel, Rita; Hajjar, Layal; Tawil, Nadim; Karam, Martin; Hamie, Maguy; Abou Merhi, Raghida; El Sabban, Marwan; El Hajj, Hiba

doi:10.3390/cancers12092483

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Lenalidomide in Combination with Arsenic Trioxide: an Effective Therapy for Primary Effusion Lymphoma

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Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut 202627, Lebanon

Department of Pathology and Laboratory Medicine, Faculty of Medicine, American University of Beirut, Beirut 202627, Lebanon

Department of Anatomy, Cell Biology, and Physiology, Faculty of Medicine, American University of Beirut, Beirut 202627, Lebanon

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Department of Experimental Pathology, Immunology, and Microbiology, Faculty of Medicine, American University of Beirut, Beirut 202627, Lebanon

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Department of Biology, Faculty of Sciences, GSBT laboratory, Lebanese University, Hadath 31143, Lebanon

Author to whom correspondence should be addressed.

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The authors contributed equally to this work.

Cancers 2020, 12(9), 2483; https://doi.org/10.3390/cancers12092483

Received: 2 July 2020 / Revised: 22 July 2020 / Accepted: 23 July 2020 / Published: 1 September 2020

(This article belongs to the Section Cancer Therapy)

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Abstract

Primary effusion lymphoma (PEL) is a rare aggressive subset of non-Hodgkin 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 for PEL and yields high response rates with no significant comorbidities. Yet, chemotherapy often fails in achieving or maintaining long-term 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 ex vivo treated PEL cells, ATO/Lena decreased the proliferation and downregulated the expression of KSHV latent viral proteins. This was associated with decreased NF-κB activation, resulting in reactivation of viral replication, downregulation of interleukin-6 (IL-6) and IL-10, 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 warrants further clinical investigation. View Full-Text

Keywords: HHV-8; immunomodulatory drugs; LANA; latent cycle; lytic cycle; lymphoma

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Moodad, S.; El Hajj, R.; Hleihel, R.; Hajjar, L.; Tawil, N.; Karam, M.; Hamie, M.; Abou Merhi, R.; El Sabban, M.; El Hajj, H. Lenalidomide in Combination with Arsenic Trioxide: an Effective Therapy for Primary Effusion Lymphoma. Cancers 2020, 12, 2483. https://doi.org/10.3390/cancers12092483

AMA Style

Moodad S, El Hajj R, Hleihel R, Hajjar L, Tawil N, Karam M, Hamie M, Abou Merhi R, El Sabban M, El Hajj H. Lenalidomide in Combination with Arsenic Trioxide: an Effective Therapy for Primary Effusion Lymphoma. Cancers. 2020; 12(9):2483. https://doi.org/10.3390/cancers12092483

Chicago/Turabian Style

Moodad, Sara, Rana El Hajj, Rita Hleihel, Layal Hajjar, Nadim Tawil, Martin Karam, Maguy Hamie, Raghida Abou Merhi, Marwan El Sabban, and Hiba El Hajj. 2020. "Lenalidomide in Combination with Arsenic Trioxide: an Effective Therapy for Primary Effusion Lymphoma" Cancers 12, no. 9: 2483. https://doi.org/10.3390/cancers12092483

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Lenalidomide in Combination with Arsenic Trioxide: an Effective Therapy for Primary Effusion Lymphoma

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