title: Circulating proteasome levels are an independent prognostic factor for survival in multiple myeloma.
abstract: 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.
authors.affiliation: Department of Hematology and Oncology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Jakob
authors.forename: Karl
authors.initials: K
authors.lastname: Egerer
authors.forename: Peter
authors.initials: P
authors.lastname: Liebisch
authors.forename: Seval
authors.initials: S
authors.lastname: Türkmen
authors.forename: Ivana
authors.initials: I
authors.lastname: Zavrski
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kuckelkorn
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heider
authors.forename: Martin
authors.initials: M
authors.lastname: Kaiser
authors.forename: Claudia
authors.initials: C
authors.lastname: Fleissner
authors.forename: Jan
authors.initials: J
authors.lastname: Sterz
authors.forename: Lorenz
authors.initials: L
authors.lastname: Kleeberg
authors.forename: Eugen
authors.initials: E
authors.lastname: Feist
authors.forename: Gerd-R
authors.initials: GR
authors.lastname: Burmester
authors.forename: Peter-M
authors.initials: PM
authors.lastname: Kloetzel
authors.forename: Orhan
authors.initials: O
authors.lastname: Sezer
mesh_terms: D005260:Female; D006262:Health; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000097:blood*; D021381:Protein Transport; D015996:Survival Rate
chemical_list: D046988:Proteasome Endopeptidase Complex