Submitted April 11, 2006
Accepted October 16, 2006
Circulating proteasome levels are an independent prognostic factor for survival in multiple myeloma
Christian Jakob, Karl Egerer, Peter Liebisch, Seval Turkmen, Ivana Zavrski, Ulrike Kuckelkorn, Ulrike Heider, Martin Kaiser, Claudia Fleissner, Jan Sterz, Lorenz Kleeberg, Eugen Feist, Gerd R. Burmester, Peter M. Kloetzel, and Orhan Sezer*
Charite-Universitatsmedizin Berlin, Germany
University Hospital Ulm, Germany
* Corresponding author; email: sezer{at}charite.de.
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 controls, 20 individuals with monoclonal gammopathies of undetermined significance (MGUS) and 141 previously untreated patients with multiple myeloma (MM) by an anti-20S proteasome ELISA. Serum proteasome concentrations were significantly elevated in MM compared to controls (P < .001), in MM versus MGUS (P = .03) and in active (n=101) versus smouldering (n=40) MM (P < .001). In patients with active MM, there was a significant (P < .001) decrease from pre- 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 (log-rank: P < .001) 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.
