Problems of Radiation Medicine and Radiobiology

Zh. M. Minchenko¹, A. D. Kustovska², S. V. Prymachenko², O. O. Dmytrenko¹, T. F. Liubarets¹,
T. Yu. Shlyahtichenko¹, V. V. Balan¹, V. G. Bebeshko¹

¹State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine», 53 Yuriia Illienka St., Kyiv, 04050, Ukraine
²National Aviation University, 1 Cosmonaut Komarov ave., Kyiv, 03058, Ukraine

IMMUNOGENETIC AND PHARMACOCHEMICAL CHARACTERIZATION OF THE ABO SYSTEM GLYCOPROTEIN PROPERTIES AS CRITERIA OF INDIVIDUAL SENSITIVITY TO ANTITUMOR AGENT BORTEZOMIB IN THE PLASMA CELL MYELOMA PATIENTS

Objective. Experimental study of the effect profile of bortezomib in the plasma cell myeloma (PCM) patients depending on a specific phenotype carrier state and a pharmacochemical characteristics of ABO system glycoproteins. Materials and methods. The research was conducted on the 104 PCM patients, including the Chornobyl NPP accident survivors (n = 49) and 65 study subjects in the comparison group. Immunogenetic criteria for positive response to the applied treatment protocols were issued according to the duration of remission, absence of infectious complications, and evidence of chronic renal failure as a disease complication.
Results. Possibility of glycoproteins A and B participation in the formation of human biological individuality at a level of protein-protein interaction with antineoplastic drug bortezomib, which is widely used in cancer management practice, in particular in the PCM treatment is considered. The glycoprotein B was shown being a selective target for bortezomib, slowing down the recognition and interaction of antigen B with monoclonal anti-B antibody, while the agglutination period lengthens at that by 66 %. Assumption that the formation of bortezomib complex with glycoprotein B provides a background for interaction with the key reaction of proteasome 26S inhibition, which to some extent contributes to the drug effect retardation was confirmed through the quantum-chemical calculations. Equilibrium is shifted toward the main reaction leading to a higher drug efficacy in patients with blood groups O (I) and A (II).
Conclusions. Since the complexation occurs predominantly in alkaline medium the administration of drugs with alkaline reaction should be restricted for at least round the clock after administration of bortezomib according to its half-life in plasma in patients with B (III) blood group and chronic renal failure.
Key words: plasma-cell myeloma, bortezomib, glycoproteins A and B, protein-protein interaction, pharmacochemical characterization, immunogenic factors.

Problems of Radiation Medicine and Radiobiology.
2019;24:426-438. doi: 10.33145/2304-8336-2019-24-426-438

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