Enzymatic activity of circulating proteasomes correlates with clinical behavior in patients with chronic lymphocytic leukemia

Wanlong Ma, Hagop Kantarjian, Susan O'Brien, Iman Jilani, Xi Zhang, Zeev Estrov, Alessandra Ferrajoli, Michael Keating, Francis Giles, Maher Albitar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

BACKGROUND. The ubiquitin-proteasome pathway has been implicated in the pathogenesis of many hematologic malignancies. METHODS. The authors measured proteasome peptidase activity levels in plasma samples from 225 patients with chronic lymphocytic leukemia (CLL) and correlated the results with clinical behavior. By using fluorogenic kinetic assays, the enzymatic activity levels of 3 proteasomes were measured: chymotrypsin-like (Ch-L), trypsin-like (Tr-L), and caspase-like (Cas-L). RESULTS. All activity levels were significantly higher in patients who had CLL compared with the levels in a control group of healthy volunteers (P < .001). Rai stage was correlated with Ch-L activity (P < .001) but not with Cas-L or Tr-L activity. Levels of β2 microglobulin (B2M) were correlated with Ch-L activity (correlation coefficient [R] = 0.4; P < .001) and with Cas-L activity (R = 0.25; P = .001) but not with Tr-L activity. Cas-L activity as a continuous variable was a strong predictor of survival. Ch-L and Cas-L activity levels as categorical variables both were strong predictors of survival; Cas-L activity was independent of B2M level but not of immunoglobulin variable heavy chain gene (IgVH) mutation status. However, the combination of elevated B2M levels (>3.2 mg/L) and Cas-L activity (>1.32 pmoL/second/mL plasma) was associated with significantly shorter survival independent of IgVH mutation status. CONCLUSIONS. The current results indicated that measuring plasma proteasome activity has prognostic value in CLL that, when combined wilh B2M, can be independent of IgVH mutation status.

Original languageEnglish (US)
Pages (from-to)1306-1312
Number of pages7
JournalCancer
Volume112
Issue number6
DOIs
StatePublished - Mar 15 2008

Keywords

  • Caspase-like
  • Chronic lymphocytic leukemia
  • Chymotrypsin-like
  • Immunoglobulin variable heavy chain gene mutation
  • Proteasome
  • Survival
  • Trypsin-like

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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