alpha-chymotrypsin and Leukemia--Lymphocytic--Chronic--B-Cell

We evaluated whether the proteasomal chymotrypsin-like (ChT-L) activity is increased in plasma of patients with acute lymphoblastic (ALL), acute myeloblastic (AML) and chronic lymphocytic (CLL) leukemias.. The activity was assayed using the fluorogenic peptide substrate in the presence of an artificial activator sodium dodecyl sulfate (SDS) in the plasma of healthy donors (n=15) and ALL (n=15), AML (n=28) and CLL (n=22) patients.. The activity was significantly (P<0.001) higher in the plasma of ALL and AML patients at the diagnosis than in healthy subjects and decreased after therapy or remained unchanged or rose during relapse. By contrast, in CLL patients at the diagnosis, the activity did not differ significantly from the healthy controls. In each group, the activity positively correlated with the serum lactic dehydrogenase activity.. Plasma proteasome ChT-L activity can be a useful bio-marker for patients with acute leukemia at the blast stage.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Chymotrypsin; Female; Humans; Hydrolysis; L-Lactate Dehydrogenase; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Acute; Male; Middle Aged; Oligopeptides; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Protein Subunits; Sodium Dodecyl Sulfate

The ubiquitin-proteasome pathway has been implicated in the pathogenesis of many hematologic malignancies.. 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).. 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 beta2 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.. The current results indicated that measuring plasma proteasome activity has prognostic value in CLL that, when combined with B2M, can be independent of IgVH mutation status.

Topics: Adult; Aged; beta 2-Microglobulin; Biomarkers, Tumor; Case-Control Studies; Caspases; Chymotrypsin; Female; Follow-Up Studies; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Variable Region; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Mutation; Prognosis; Proteasome Endopeptidase Complex; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Survival Rate; Trypsin