Expression of receptor activator of nuclear factor kappaB ligand on bone marrow plasma cells correlates with osteolytic bone disease in patients with multiple myeloma.
OBJECTIVE
Increased bone resorption is a hallmark of multiple myeloma and is attributable to osteoclast activation. Recent studies showed that the receptor activator of nuclear factor kappaB ligand (RANKL) is the key mediator of osteoclastogenesis and plays a crucial role in bone destruction in malignant bone disease. We found that human myeloma cells express RANKL and analyzed the association of the RANKL expression with the presence of osteolytic bone disease in patients with multiple myeloma.


METHODS
Flow cytometry was performed on bone marrow samples derived from controls and multiple myeloma patients with or without osteolytic bone lesions on conventional radiography. Plasma cells were identified as CD38++/CD138+ cells. The level of RANKL expression on the surface of bone marrow plasma cells was correlated with the bone status of the patients.


RESULTS
The bone marrow plasma cells from controls showed no or only a weak surface expression of RANKL, and the median mean fluorescence index (MFI) was 6. In contrast, expression of RANKL could be detected on bone marrow plasma cells from all of the patients with multiple myeloma, and median MFI was 47. The difference in MFI for RANKL expression of bone marrow plasma cells from controls and myeloma patients was highly significant (P < 0.0005). Myeloma patients with osteolytic bone lesions showed a significantly higher expression of RANKL (median MFI = 60; range, 16-2494) compared with patients without osteolysis (median MFI = 16; range, 6-229; P < 0.0005).


CONCLUSIONS
These results show for the first time that the level of RANKL expression by myeloma cells correlates significantly with osteolytic bone disease.
Heider
Ulrike
U
Department of Oncology and Hematology, Universitätsklinikum Charité, Berlin 10098, Germany.
Langelotz
Corinna
C
Jakob
Christian
C
Zavrski
Ivana
I
Fleissner
Claudia
C
Eucker
Jan
J
Possinger
Kurt
K
Hofbauer
Lorenz C
LC
Sezer
Orhan
O
D036541:ADP-ribosyl Cyclase / Q000096:biosynthesis; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis; D001847:Bone Diseases / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism*; D010014:Osteolysis / Q000378:metabolism*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B
D015703:Antigens, CD; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1