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Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-02-0546. This Article Full Text (PDF) All Versions of this Article: 2003-02-0546v1 103/1/258    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 Wang, E. S Articles by Moore, M. A S Search for Related Content PubMed PubMed Citation Articles by Wang, E. S Articles by Moore, M. A S Social Bookmarking                   What's this? Submitted February 19, 2003 Accepted August 28, 2003 Telomerase inhibition with an oligonucleotide telomerase template antagonist: in vitro and in vivo studies in multiple myeloma and lymphoma Eunice S Wang, Kaida Wu, Allison C Chin, Selina Chen-Kiang, Krisztina Pongracz, Sergei Gryaznov, and Malcolm A S Moore* Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Geron Corp., Menlo Park, CA, USA Departments of Pathology and Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA Leukemia Service, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA * Corresponding author; email: m-moore{at}ski.mskcc.org. The efficacy of telomerase inhibition with an oligonucleotide N3'P5' thio-phosphoramidate (GRN163) complementary to the RNA template region of telomerase was examined on human multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) cell lines, primary MM cells, and tumor xenografts. GRN163 treatment reduced telomerase levels in all cells and induced more rapid telomeric shortening. Continuous GRN163 treatment over 7-14 days resulted in proliferative arrest, morphological changes, and apoptosis characteristic of cell crisis in tumor cell lines with short (1.7- 5.4 Kb) but not long (9-11 Kb) telomeres. Intratumoral administration of GRN163 also inhibited the growth of MM and NHL xenografts established from cell lines with short telomeres (Hs602 lymphoma 2.7 Kb, CAG myeloma 2.7 Kb) and increased tumor apoptosis. However, GRN163 therapy of NHL xenografts established from cells with long telomeres (11.0 Kb) had equivocal effects on tumor growth and did not induce apoptosis over this time frame. Systemic daily intraperitoneal administration of GRN163 in myeloma xenografts with short telomere lengths also decreased tumor telomerase levels and reduced tumor volumes. These data demonstrate that telomerase is important for the replication of mature B cell neoplasia by stabilizing short telomeres and suggest that telomerase inhibition represents a novel therapeutic approach for MM and NHL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. R. Jackson, C.-H. Zhu, V. Paulson, L. Watkins, Z. G. Dikmen, S. M. Gryaznov, W. E. Wright, and J. W. Shay Antiadhesive Effects of GRN163L--An Oligonucleotide N3'->P5' Thio-Phosphoramidate Targeting Telomerase Cancer Res., February 1, 2007; 67(3): 1121 - 1129. [Abstract] [Full Text] [PDF] A. E. Hochreiter, H. Xiao, E. M. Goldblatt, S. M. Gryaznov, K. D. Miller, S. Badve, G. W. Sledge, and B.-S. Herbert Telomerase Template Antagonist GRN163L Disrupts Telomere Maintenance, Tumor Growth, and Metastasis of Breast Cancer. Clin. Cancer Res., May 15, 2006; 12(10): 3184 - 3192. [Abstract] [Full Text] [PDF]

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