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

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Abstract

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.

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Abbreviations

BM:

bone marrow

CFU-F:

colony-forming unit of fibroblasts

DLBCL:

diffuse large B-cell lymphoma

IFN-γ:

interferon gamma

IL:

interleukin

MFI:

mean fluorescence intensity

MSC:

multipotent mesenchymal stromal cells

PDT:

population doubling time

REL:

relative expression level

TNF-α:

tumor necrosis factor alpha

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Acknowledgements

The authors are grateful to O. Pshenichnikova for a productive discussion of the materials of this work.

Funding

This work was supported by the Russian Foundation for Basic Research (project no. 17-04-00170).

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Authors and Affiliations

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

    Nataliya A. Petinati, Alexey E. Bigildeev, Dmitriy S. Karpenko, Natalia V. Sats, Nikolay M. Kapranov, Yulia O. Davydova, Ekaterina A. Fastova, Aminat U. Magomedova, Sergey K. Kravchenko, Nina I. Drize & Valeriy G. Savchenko

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

    Georgiy P. Arapidi & Maria M. Lagarkova

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

    Georgiy P. Arapidi

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

    Georgiy P. Arapidi

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

    Maria I. Rusanova

Authors
  1. Nataliya A. Petinati
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Corresponding author

Correspondence to Nataliya A. Petinati.

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The authors declare no conflict of interest in financial or any other sphere. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Petinati, N.A., Bigildeev, A.E., Karpenko, D.S. et al. Humoral Effect of a B-Cell Tumor on the Bone Marrow Multipotent Mesenchymal Stromal Cells. Biochemistry Moscow 86, 207–216 (2021). https://doi.org/10.1134/S0006297921020097

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  • DOI: https://doi.org/10.1134/S0006297921020097

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