Abstract

Molecular Changes in Immunological Characteristics of Bone Marrow Multipotent Mesenchymal Stromal Cells in Lymphoid Neoplasia

Nataliya A. Petinati^1,a*^#, Aleksandra V. Sadovskaya^1,2#, Natalia V. Sats¹, Nikolai M. Kapranov¹, Yulia O. Davydova¹, Ekaterina A. Fastova¹, Aminat U. Magomedova¹, Anastasia N. Vasilyeva¹, Olga A. Aleshina¹, Georgiy P. Arapidi^3,4,5, Viktoria O. Shender^3,4, Igor P. Smirnov³, Olga V. Pobeguts³, Maria A. Lagarkova³, Nina I. Drize¹, and Elena N. Parovichnikova¹

¹National Medical Research Center for Hematology, Ministry of Health of the Russian Federation, 125167 Moscow, Russia

²Lomonosov Moscow State University, 119991 Moscow, Russia

³Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, 119435 Moscow, Russia

⁴Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia

⁵Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia

Received September 15, 2023; Revised November 22, 2023; Accepted November 23, 2023
Immune system and bone marrow stromal cells play an important role in maintaining normal hematopoiesis. Lymphoid neoplasia disturbs not only development of immune cells, but other immune response mechanisms as well. Multipotent mesenchymal stromal cells (MSCs) of the bone marrow are involved in immune response regulation through both intercellular interactions and secretion of various cytokines. In hematological malignancies, the bone marrow stromal microenvironment, including MSCs, is altered. Aim of this study was to describe the differences of MSCs’ immunological function in the patients with acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). In ALL, malignant cells arise from the early precursor cells localized in bone marrow, while in DLBCL they arise from more differentiated B-cells. In this study, only the DLBCL patients without bone marrow involvement were included. Growth parameters, surface marker expression, genes of interest expression, and secretion pattern of bone marrow MSCs from the patients with ALL and DLBCL at the onset of the disease and in remission were studied. MSCs from the healthy donors of corresponding ages were used as controls. It has been shown that concentration of MSCs in the bone marrow of the patients with ALL is reduced at the onset of the disease and is restored upon reaching remission; in the patients with DLBCL this parameter does not change. Proliferative capacity of MSCs did not change in the patients with ALL; however, the cells of the DLBCL patients both at the onset and in remission proliferated significantly faster than those from the donors. Expression of the membrane surface markers and expression of the genes important for differentiation, immunological status maintenance, and cytokine secretion differed significantly in the MSCs of the patients from those of the healthy donors and depended on nosology of the disease. Secretomes of the MSCs varied greatly; a number of proteins associated with immune response regulation, differentiation, and maintenance of hematopoietic stem cells were depleted in the secretomes of the cells from the patients. Lymphoid neoplasia leads to dramatic changes in the functional immunological status of MSCs.
KEY WORDS: multipotent mesenchymal stromal cells, acute lymphoblastic leukemia, diffuse large B-cell lymphoma, gene expression, protein secretion
DOI: 10.1134/S0006297924050092
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