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Blood, 1 March 2007, Vol. 109, No. 5, pp. 2100-2105.
Prepublished online as a Blood First Edition Paper on November 9, 2006; DOI 10.1182/blood-2006-04-016360.
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NEOPLASIA
Circulating proteasome levels are an independent prognostic factor for survival in multiple myeloma
Christian Jakob1,
Karl Egerer2,
Peter Liebisch3,
Seval Türkmen4,
Ivana Zavrski1,
Ulrike Kuckelkorn5,
Ulrike Heider1,
Martin Kaiser1,
Claudia Fleissner1,
Jan Sterz1,
Lorenz Kleeberg1,
Eugen Feist2,
Gerd-R. Burmester2,
Peter-M. Kloetzel5, and
Orhan Sezer1
1 Department of Hematology and Oncology, Charité-Universitätsmedizin Berlin, Germany;
2 Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Germany;
3 Department of Hematology and Oncology, Universitätsklinikum Ulm, Germany;
4 Department of Tumorcytogenetics, Charité-Universitätsmedizin Berlin, Germany;
5 Department of Biochemistry, Charité-Universitätsmedizin Berlin, Germany
The proteasome is a proteolytic complex for intracellular degradation of ubiquitinated proteins which are involved in cell-cycle regulation and apoptosis. A constitutively increased proteasome activity has been found in myeloma cells. We studied circulating proteasome levels and their prognostic significance in sera of 50 control subjects, 20 persons with monoclonal gammopathies of undetermined significance (MGUS), and 141 previously untreated patients with multiple myeloma (MM) by an anti-20S proteasome enzyme-linked immunoabsorbent assay (ELISA). Serum proteasome concentrations were significantly elevated in MM compared with controls (P < .001), in MM versus MGUS (P = .03), and in active (n = 101) versus smoldering (n = 40) MM (P < .001). In patients with active MM, there was a significant (P < .001) decrease from pretreatment to post-treatment proteasome concentrations in responders to chemotherapy, but not in nonresponders. Circulating proteasome levels were identified as a prognostic factor for overall survival in the univariate (P < .001 log-rank test) and in the multivariate (hazard ratio, 4.38) survival analysis in patients with active MM. We demonstrate for the first time that increased serum proteasome concentrations correlate with advanced disease and are an independent prognostic factor in MM.
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