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Blood, 15 December 2008, Vol. 112, No. 13, pp. 5180-5189. Prepublished online as a Blood First Edition Paper on September 4, 2008; DOI 10.1182/blood-2008-01-133108. This Article Full Text (PDF) Erratum (v114,p3506) All Versions of this Article: blood-2008-01-133108v1 112/13/5180    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lapalombella, R. Articles by Byrd, J. C Search for Related Content PubMed PubMed Citation Articles by Lapalombella, R. Articles by Byrd, J. C Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 10, 2008 Accepted June 22, 2008 Lenalidomide down-regulates the CD20 antigen and antagonizes direct and antibody-dependent cellular cytotoxicity of rituximab on primary chronic lymphocytic leukemia cells Rosa Lapalombella, Bo Yu, Georgia Triantafillou, Qing Liu, Jonathan P Butchar, Gerard Lozanski, Asha Ramanunni, Lisa L. Smith, William Blum, Leslie Andritsos, Da-Sheng Wang, Amy Lehman, Ching-Shih Chen, Amy J. Johnson, Guido Marcucci, Robert J. Lee, L. James Lee, Susheela Tridandapani, Natarajan Muthusamy, and John C Byrd* Hematology-Oncology, Department of Medicine, The Ohio State University, Columbus, OH, United States Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, United States Division of Phamaceutics, The Ohio State University, Columbus, OH, United States Division of Pulmonary Medicine, The Ohio State University, Columbus, OH, United States Department of Pathology, The Ohio State University, Columbus, OH, United States Medicinal Chemistry, The Ohio State University, Columbus, OH, United States Biostatistical Core, The Ohio State University, Columbus, OH, United States Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH, United States * Corresponding author; email: john.byrd{at}osumc.edu. Lenalidomide, an immunomodulatory agent that enhances antibody dependent cellular cytotoxicity (ADCC), is currently being investigated as a therapy for chronic lymphocytic leukemia (CLL). The anti-CD20 antibody rituximab is active in CLL and represents a rational agent to combine with lenalidomide. We therefore examined if lenalidomide combined with rituximab enhances direct apoptosis and antibody dependent cellular cytoxicity (ADCC) in CLL cells. In contrast to previous reports using CD20-positive lymphoma cell lines, lenalidomide down-regulated CD20 surface antigen expression in CLL patient cells via enhanced internalization, without influencing transcription. The CD20 surface antigen internalization enhanced delivery of an oligonucleotide incorporated into anti-CD20 immunoliposomes. In addition, CD20 surface antigen down-modulation by lenalidomide in CLL was accompanied by diminished rituximab-mediated apoptosis and ADCC. These observations suggest a need for alternative sequencing strategies to avoid antagonism between lenalidomide and rituximab therapy in CLL. Additionally, they suggest that lenalidomide therapy might be useful to enhance targeted delivery of RNAi-based therapies using CD20 immunoliposomes in B-cell malignancies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The yin and yang of lenalidomide Neil E. Kay Blood 2008 112: 4785-4786. [Full Text] [PDF] This article has been cited by other articles: A. G. Ramsay and J. G. Gribben Immune dysfunction in chronic lymphocytic leukemia T cells and lenalidomide as an immunomodulatory drug Haematologica, September 1, 2009; 94(9): 1198 - 1202. [Full Text] [PDF]

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