No abstract

The ubiquitin-proteasome system is relevant in the pathobiology of many haematological malignancies, including multiple myeloma. The assessment of proteasome concentration and chymotrypsin-like (ChT-L) activity might constitute a new approach to diagnosis, prognosis and monitoring of anticancer treatment of patients with haematological malignancies and other diseases. The aim of our study was to determine which material, plasma or serum, is better for measuring chymotrypsin-like (ChT-L) activity and proteasome concentration. We analysed proteasome concentration and chymotrypsin-like (ChT-L) activity in 70 plasma and serum samples drawn from 28 patients at different treatment stages for multiple myeloma (MM) and 31 healthy volunteers. Proteasome ChT-L activity and concentration in multiple myeloma patients were significantly higher in plasma compared to serum. In this group we observed significant and positive correlations both between the plasma and serum proteasome ChT-L activity and plasma and serum proteasome concentration. The higher values of proteasome concentration and ChT-L activity in plasma than in serum and their better correlations with parameters of tumour load and prognosis suggest that plasma constitutes a better biological material for measuring ChT-L activity and proteasome concentration than serum in multiple myeloma patients.

Proteasome inhibitors (PIs) such as bortezomib constitute an important part of the modern standard therapy for multiple myeloma (MM). In this study, we set out to assess whether proteasome concentration and chymotrypsin-like (ChT-L) activity could serve as potential biomarkers defining the likelihood of response to treatment with bortezomib, in order to identify patients who are more likely to respond to treatment with PI. We analysed proteasome concentration and ChT-L activity in the plasma of 78 patients with newly diagnosed MM during treatment with or without proteasome inhibitors. Values of all the studied parameters in the group of responders decreased sharply from the initial levels already after the third cycle of chemotherapy and remained significantly lower until the end of treatment. On the other hand, in the group of non-responders, there was an increase in the measured proteasome parameters already after the third cycle, and they remained high during the next cycles of therapy. We also showed that high baseline proteasome ChT-L activity values might prognosticate longer progression-free survival (PFS) in patients treated with PI. Our findings demonstrate that measuring plasma proteasome ChT-L activity can be used as a powerful biomarker for predicting clinical response to treatment and PFS in patients with newly diagnosed MM.