Myeloma cell expression of 10 candidate genes for osteolytic bone disease. Only overexpression of DKK1 correlates with clinical bone involvement at diagnosis.
Osteolytic bone disease (OBD) in multiple myeloma (MM) is caused by interactions between MM cells and the bone marrow microenvironment and is characterized by increased osteoclastic bone resorption and decreased osteoblastic bone formation. Recently, the role of osteoblast inhibition has come into focus, especially the possible role of overexpression of DKK1, an inhibitor of the Wnt signalling pathway. Further, CKS2, PSME2 and DHFR have also been reported as candidate genes for OBD. We studied the gene expression by quantitative reverse transcription polymerase chain reaction of TNFSF11 (RANKL), TNFSF11A (RANK), TNFRSF11B (OPG), CCL3 (MIP1A), CCL4 (MIP1B), PTHR1 (PTHrp), DKK1, CKS2, PSME2 and DHFR in purified, immunophenotypic FACS-sorted plasma cells from 171 newly diagnosed MM patients, 20 patients with monoclonal gammopathy of undetermined significance and 12 controls. The gene expressions of the analysed genes were correlated with radiographically assessed OBD. Only overexpression of DKK1 was correlated to the degree of OBD. Myeloma cells did not express TNFSF11A, TNFSF11, or TNFRSF11B, and very rarely expressed CCL3 and PTHR11. CCL4, CKS2, PSME2 and DHFR were variably expressed, but the expression of these genes showed no correlation with OBD. In contrast, loss of PSME2 expression in MM plasma cells was significantly correlated with OBD.
Haaber
Jacob
J
Department of Pathology, Odense University Hospital, Odense, Denmark. haaber@dadlnet.dk
Abildgaard
Niels
N
Knudsen
Lene Meldgaard
LM
Dahl
Inger Marie
IM
Lodahl
Marianne
M
Thomassen
Mads
M
Kerndrup
Gitte Birk
GB
Rasmussen
Thomas
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism; D054407:Chemokine CCL4 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D010014:Osteolysis / Q000235:genetics* / Q000378:metabolism; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D010950:Plasma Cells / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism
C515429:CCL3 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D054405:Chemokine CCL3; D054407:Chemokine CCL4; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D053244:Osteoprotegerin; C473449:PTH1R protein, human; D053246:Receptor Activator of Nuclear Factor-kappa B; D044168:Receptor, Parathyroid Hormone, Type 1; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; D013762:Tetrahydrofolate Dehydrogenase; D011494:Protein Kinases; D042846:CDC2-CDC28 Kinases; C083689:CKS2 protein, human; C486207:PSME2 protein, human; D046988:Proteasome Endopeptidase Complex