Haematologica 2003 - Supplements
Haematologica 2003 - Supplements Haematologica 2003 - Supplements
151 A Role for a Soluble Form of the Ligand for Receptor Activator of NFB (sRANKL) in the Development of Myeloma Bone Disease: Lessons from Murine Models of Myeloma. Peter I. Croucher*, Evy De Leenheer*‡, Gabrielle Mueller*, Mark Perry§, Sandy Cordiner-Lawrie*, Ben Van Camp‡, Karin Vanderkerken‡ *Nuffield Department of Orthopaedic Surgery, University of Oxford, Nuffield Orthopaedic Centre, Oxford, OX3 7LD UK. ‡Dept of Hematology and Immunology, Free University Brussels (VUB), Brussels, Belgium. §Dept of Anatomy, University of Bristol, UK. Multiple myeloma is associated with the development of a bone disease, which is mediated by increased osteoclastic bone resorption. Until recently, the factors responsible for stimulating the increased osteoclast formation have been unknown. The identification of the ligand for receptor activator of NFB (RANKL) and the demonstration that RANKL plays a critical role in normal osteoclast formation has raised the possibility that abnormal expression of this molecule may contribute to osteoclast formation in myeloma. RANKL exists principally as a membrane-bound molecule, although a soluble form (sRANKL) can be produced. The aim of this study was to determine whether sRANKL was associated with increased osteoclast formation and the development of myeloma bone disease in the 5T2MM and 5T33MM syngeneic models of myeloma. Male C57BL/KaLwRijHsd mice were injected with 5T2MM or 5T33MM cells, or left un-injected. The myeloma disease was allowed to develop, which took 12 weeks in 5T2MM-bearing mice and 4 weeks in 5T33MM-bearing mice. At these points animals in each group, including the respective un-injected control groups (naïve), were sacrificed. sRANKL and the decoy receptor, osteoprotegerin (OPG), were measured by ELISA and the bone disease was assessed by a combination of radiographaphic, densitometric and histological analyses. Soluble RANKL was detected in the serum of mice bearing 5T2MM cells (379±58.4pg/ml) but not in the serum of naïve mice or mice bearing 5T33MM cells. Serum concentrations of OPG in naïve animals and 5T2MM bearing animals were not significantly different (1.77±0.13ng/ml vs 1.86±0.08ng/ml, respectively). However, OPG was higher in mice bearing 5T33MM cells when compared to naïve animals (14.97±1.09ng/ml vs 1.33±0.13ng/ml, respectively, p
tibia (con=49.1±0.7mg/cm2 vs 5T2=47.1±1.17mg/cm2). Treatment of mice, from the time of 5T2MM cell injection, with RANK.Fc prevented the development of lytic bone lesions in the long bones (5T2=8.2±1.5 vs 5T2+RANK.Fc=0±0, p
- Page 113 and 114: clusters were found, the first was
- Page 115 and 116: MGUS but most likely not crucial fo
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- Page 119 and 120: 4 patients had MMSET/IgH but did no
- Page 121 and 122: and clonal PC from MGUS, MM and PCL
- Page 123 and 124: 059 VEGF receptor expresion in Mult
- Page 125 and 126: two HLA-A2+ myeloma patients with C
- Page 127 and 128: molecules expressed on the surface
- Page 129 and 130: Recognition of these antigens appea
- Page 131 and 132: Diagnosis requires a single area of
- Page 133 and 134: 081 Incidence of solid tumors in co
- Page 135 and 136: Growth Factor (VEGF), Hepatocyte Gr
- Page 137 and 138: PC-AI levels of MGUS and SMM patien
- Page 139 and 140: 093 The predominant pathway of tran
- Page 141 and 142: was associated with I.V. line, whil
- Page 143 and 144: 103 Vascular amyloidosis induces se
- Page 145 and 146: 5. Signal transduction pathways and
- Page 147 and 148: integrin in IGF-1-triggered MM cell
- Page 149 and 150: 118 IL-6- Induced Phosphorylation o
- Page 151 and 152: 123 THE IGF/IGF-1R SYSTEM IS A MAJO
- Page 153 and 154: human myeloma cell line (HMCL) to a
- Page 155 and 156: ligation or dexamethasone (Georgii-
- Page 157 and 158: 6. Role of microenvironment 6.1 Cel
- Page 159 and 160: 141 Human myeloma cells adhere to f
- Page 161 and 162: 145 STUDY OF BONE MARROW ANGIOGENES
- Page 163: patients, the growth of primary mye
- Page 167 and 168: 157 The Nitrogen-Containing Bisphos
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- Page 171 and 172: atio of >3. This system has subdivi
- Page 173 and 174: Patient 1 (IgG/κ);IgG - 16.5 days,
- Page 175 and 176: 176 Pro-inflammatory and angiogenic
- Page 177 and 178: 180 Clinical study on the bone lesi
- Page 179 and 180: 7.2 Imaging studies 185 99mTc-MIBI
- Page 181 and 182: 189 Factors Predicting Occult Spina
- Page 183 and 184: vivo detected resonances was invest
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- Page 187 and 188: (β2m) & C reactive protein (CRP).
- Page 189 and 190: plasmids carrying the clonotypic in
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- Page 193 and 194: 216 Transgenic expression of Myc an
- Page 195 and 196: 221 Prolonged survival in the 5T2MM
- Page 197 and 198: 9. Chemotherapy, maintenance, treat
- Page 199 and 200: 229 EFFECTIVENESS OF STANDARD CHEMO
- Page 201 and 202: 234 Melphalan and Dexamethasone- Is
- Page 203 and 204: Methods. We investigated the VECD p
- Page 205 and 206: 9.2 Renal complications. 243 MERIT
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- Page 209 and 210: those with Hb >13 g/dL. Analysis of
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tibia (con=49.1±0.7mg/cm2 vs 5T2=47.1±1.17mg/cm2).<br />
Treatment of mice, from the time of 5T2MM cell injection, with<br />
RANK.Fc prevented the development of lytic bone lesions in the<br />
long bones (5T2=8.2±1.5 vs 5T2+RANK.Fc=0±0, p
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