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Humoral Effect of a B-Cell Tumor on the Bone Marrow Multipotent Mesenchymal Stromal Cells

Nataliya A. Petinati1,a*, Alexey E. Bigildeev1, Dmitriy S. Karpenko1, Natalia V. Sats1, Nikolay M. Kapranov1, Yulia O. Davydova1, Ekaterina A. Fastova1, Aminat U. Magomedova1, Sergey K. Kravchenko1, Georgiy P. Arapidi2,3,4, Maria I. Rusanova5, Maria M. Lagarkova2, Nina I. Drize1, and Valeriy G. Savchenko1

1National Research Center for Hematology, Ministry of Health, 125167 Moscow, Russia

2Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, 119435 Moscow, Russia

3Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia

4Moscow Institute of Physics and Technology (State University), 141700 Dolgoprudny, Moscow Region, Russia

5Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

* To whom correspondence should be addressed.

Received July 30, 2020; Revised September 14, 2020; Accepted September 14, 2020
The properties of bone marrow (BM)-derived multipotent mesenchymal stromal cells (MSCs) are altered in the patients with the diffuse large B cell lymphoma (DLBCL) without BM involvement. It was suggested that plasma from the patients contains soluble factors that affect MSCs. Plasma and BM-derived MSCs from the DLBCL patients at the onset of the disease and one month after the end of treatment were studied. Concentration of the plasma cytokines and gene expression in the MSCs were evaluated by the Bio-Plex Pro Human Cytokine Panel kit to measure 27 analytes and real-time PCR. Plasma and MSCs from the healthy donors were used as controls. Analysis of cytokines in the plasma from healthy donors and patients before and one month after the end of treatment revealed significant differences in the concentration of 14 out of 27 cytokines. Correlations between the levels of secreted cytokines were altered in the plasma from patients indicating that the immune response regulation was disturbed. Cultivation of the MSCs from the healthy donors in the medium supplemented with the plasma from patients led to the changes in the MSC properties, similar to those observed in the MSCs from patients. The BM-derived MSCs were shown to participate in the humoral changes occurring in the DLBCL patients. For the first time, it was shown that the precursors of the stromal microenvironment – multipotent mesenchymal stromal cells – are altered in the patients with DLBCL without bone marrow involvement due to the humoral effect of the tumor and the response of organism to it. Comprehensive analysis of the results shows that, when remission is achieved in the patients with DLBCL, composition of the plasma cytokines normalizes, but does not reach the level observed in the healthy donors. The discovery of a new aspect of the effect of the tumor B-cells on the organism could help to reveal general regularities of the humoral effect of various tumors on the bone marrow stromal cells.
KEY WORDS: DLBCL, MSCs, cytokines, chemokines, secretion

DOI: 10.1134/S0006297921020097