Plasma Proteasome Level is a Potential Marker in Patients with Solid Tumors and Hemopoietic Malignancies

BACKGROUND. Proteasomes are nonlysosomal proteolytic structures that have b een implicated in cell growth and differentiation. Abnormal expression leve ls of proteasomes have been described in tumor cells, and proteasomes can b e detected and measured in plasma. The objective of this study was to chara cterize differences in proteasome levels between normal, healthy donors and patients with neoplastic disease and to correlate the findings with clinic al status and other biologic markers of disease spread. METHODS. Plasma proteasome levels were measured using a sandwich enzyme-lin ked immunosorbent assay in normal donors (n = 73 donors) and in patients wi th solid tumors (n = 20 patients), acute leukemia (n = 35 patients), myelop roliferative (n = 37 patients) and myelodysplastic (n = 19 patients) syndro mes, chronic lymphocytic leukemia (n = 44 patients), non-Hodgkin lymphoma ( n = 104 patients), Hodgkin disease (n = 14 patients), other lymphoid disord ers (n = 17 patients), and multiple myeloma (n = 27 patients). RESULTS. in the normal donors, the plasma proteasome concentration was 2356 ng/mL +/- 127 ng/mL. Patients with solid tumors exhibited a significantly higher value (7589 ng/mL +/- 2124 ng/mL), similar to the patients with myel oproliferative (4099 ng/mL +/- 498 ng/mL) and myelodysplastic (2922 ng/mL /- 322 ng/mL) syndromes. Patients with lymphoproliferative disorders, in co ntrast, had significantly lower values than normal donors (1751 ng/mL +/- 1 07 ng/mL), except those in aggressive phase of the disease. This low level persisted in patients who were in complete remission. Proteasome levels dec reased during the initial phase of treatment. Although there was a signific ant correlation with serum lactic dehydrogenase levels, frequent discrepanc ies were noted. There was no correlation with C-reactive protein or beta2-m icroglobulin levels, even in the group of patients with multiple myeloma. CONCLUSIONS. The plasma proteasome level is a potential new tool for the mo nitoring of patients with neoplastic disease. It is not correlated solely w ith cell lysis and may be involved in the pathophysiology of disease progre ssion. (C) 2001 American Cancer Society.