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Prepublished online as a Blood First Edition Paper on April 10, 2003; DOI 10.1182/blood-2003-02-0380. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-02-0380v1 102/3/1064    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Terpos, E. Articles by Rahemtulla, A. Search for Related Content PubMed PubMed Citation Articles by Terpos, E. Articles by Rahemtulla, A. Related Collections Neoplasia Signal Transduction Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2003, Vol. 102, No. 3, pp. 1064-1069 NEOPLASIA Soluble receptor activator of nuclear factor B ligand–osteoprotegerin ratio predicts survival in multiple myeloma: proposal for a novel prognostic index Evangelos Terpos, Richard Szydlo, Jane F. Apperley, Evdoxia Hatjiharissi, Marianna Politou, John Meletis, Nora Viniou, Xenophon Yataganas, John M. Goldman, and Amin Rahemtulla From the Department of Hematology, Faculty of Medicine Imperial College, Hammersmith Hospital, London, United Kingdom; the Department of Hematology, Theagenion Cancer Center, Thessaloniki, Greece; and the First Department of Medicine, University of Athens School of Medicine, Laikon Hospital, Greece Interaction between receptor activator of nuclear factor B ligand (RANKL) and RANK/osteoprotegerin (OPG) plays a dominant role in osteoclast activation and possibly in plasma cell survival in multiple myeloma (MM). We measured soluble RANKL (sRANKL), OPG, and bone remodeling markers in 121 patients with newly diagnosed MM to evaluate their role in bone disease and survival. Serum levels of sRANKL were elevated in patients with MM and correlated with bone disease. The sRANKL/OPG ratio was also increased and correlated with markers of bone resorption, osteolytic lesions, and markers of disease activity. The sRANKL/OPG ratio, C-reactive protein (CRP), and 2-microglobulin were the only independent prognostic factors predicting survival in multivariate analysis. We generated a prognostic index based on these factors that divided our patients into 3 risk groups. The low-risk group had a 96% probability of survival at 5 years, whereas the intermediate-risk and the high-risk groups had probabilities of survival of 52% and 0%, respectively. Not only do these results confirm for the first time in humans the importance of sRANKL/OPG in the development of bone disease, they also highlight the role of this pathway in the biology of plasma cell growth as reflected by its influence on survival. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Prognostic staging in myeloma: in search of biology A. K. Stewart Blood 2003 102: 778-779. [Full Text] [PDF] This article has been cited by other articles: M. K. Crook and T. A. Guise RANKL: Targeting Bone and Cancer to Treat Skeletal Complications of Malignancy IBMS BoneKEy, September 1, 2009; 6(9): 323 - 338. [Abstract] [Full Text] [PDF] E. TERPOS, M. KIAGIA, E. M. KARAPANAGIOTOU, A. CHARPIDOU, K. D. DILANA, E. NASOTHIMIOU, K. J. HARRINGTON, A. POLYZOS, and K. N. SYRIGOS The Clinical Significance of Serum Markers of Bone Turnover in NSCLC Patients: Surveillance, Management and Prognostic Implications Anticancer Res, May 1, 2009; 29(5): 1651 - 1657. [Abstract] [Full Text] [PDF] F. Silvestris, S. Ciavarella, M. De Matteo, M. Tucci, and F. Dammacco Bone-Resorbing Cells in Multiple Myeloma: Osteoclasts, Myeloma Cell Polykaryons, or Both? Oncologist, March 1, 2009; 14(3): 264 - 275. [Abstract] [Full Text] [PDF] O. Sezer Myeloma Bone Disease: Recent Advances in Biology, Diagnosis, and Treatment Oncologist, March 1, 2009; 14(3): 276 - 283. [Abstract] [Full Text] [PDF] Y.-W. Qiang, Y. Chen, O. Stephens, N. Brown, B. Chen, J. Epstein, B. Barlogie, and J. D. Shaughnessy Jr Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma Blood, July 1, 2008; 112(1): 196 - 207. [Abstract] [Full Text] [PDF] A. E. Kearns, S. Khosla, and P. J. Kostenuik Receptor Activator of Nuclear Factor {kappa}B Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease Endocr. Rev., April 1, 2008; 29(2): 155 - 192. [Abstract] [Full Text] [PDF] R. N. Pearse Wnt antagonism in multiple myeloma: a potential cause of uncoupled bone remodeling. Clin. Cancer Res., October 15, 2006; 12(20): 6274s - 6278s. [Abstract] [Full Text] [PDF] T. Wakita, M. Mogi, K. Kurita, M. Kuzushima, and A. Togari Increase in RANKL: OPG Ratio in Synovia of Patients with Temporomandibular Joint Disorder Journal of Dental Research, July 1, 2006; 85(7): 627 - 632. [Abstract] [Full Text] [PDF] J.-J. Body, T. Facon, R. E. Coleman, A. Lipton, F. Geurs, M. Fan, D. Holloway, M. C. Peterson, and P. J. Bekker A Study of the Biological Receptor Activator of Nuclear Factor-{kappa}B Ligand Inhibitor, Denosumab, in Patients with Multiple Myeloma or Bone Metastases from Breast Cancer Clin. Cancer Res., February 15, 2006; 12(4): 1221 - 1228. [Abstract] [Full Text] [PDF] C Van Poznak, S S Cross, M Saggese, C Hudis, K S Panageas, L Norton, R E Coleman, and I Holen Expression of osteoprotegerin (OPG), TNF related apoptosis inducing ligand (TRAIL), and receptor activator of nuclear factor {kappa}B ligand (RANKL) in human breast tumours J. Clin. Pathol., January 1, 2006; 59(1): 56 - 63. [Abstract] [Full Text] [PDF] A. Rogers and R. Eastell Circulating Osteoprotegerin and Receptor Activator for Nuclear Factor {kappa}B Ligand: Clinical Utility in Metabolic Bone Disease Assessment J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6323 - 6331. [Abstract] [Full Text] [PDF] E. Terpos and M.-A. 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