Altered balance between proteolysis and antiproteolysis in oncohematologic diseases

Abstract

Destruction of malignant cell clones and search for markers of the effectiveness of chemotherapy in patients with hematologic malignancies is an urgent direction of research. The purpose of this paper was to study plasma of patients with various forms of blood tumor, the activity of trypsin-like enzymes, matrix metalloproteinases MMP2 and MMP9, content of α1-proteinase inhibitor and α2-macroglobulin before and after the cytotoxic therapy by anthracycline antibiotics, doxorubicin and daunorubicin. It was established that concentration of inhibitors and activity of trypsin-like enzymes increased in patients with acute myeloid leukemia and multiple myeloma against the backdrop of multidirectional changes of proMMP9. Activity of the latter enzyme was reduced to 0,03±0,01 rel. u. in acute myeloid leukemia, and after chemotherapy it increased 7 times. Reducing level of inhibitors and increasing activity of MMP9 were found in chronic lymphocytic leukemia. The presence of the correlation between the α2-macroglobulin and gelatinase activity in the treatment indicates that the inhibitor is an important mechanism for storing of gelatinоlytic potential. Balance between proteolysis and antiproteolysis depends on the type of proliferating cells and the course of the disease. Indicators of tissue destruction may be an additional criterion for monitoring the stage of blood tumors and efficacy of treatment.

Keywords

• degradation of proteins
• acute myeloid leukemia
• chronic lymphocytic leukemia
• multiple myeloma
• anthracycline antibiotics