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 (IgV~H~) 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 IgV~H~ mutation status.
CONCLUSIONS
The current results indicated that measuring plasma proteasome activity has prognostic value in CLL that, when combined with B2M, can be independent of IgV~H~ mutation status. Cancer 2008. © 2008 American Cancer Society.