| Autor: |
Petinati NA; National Medical Research Center for Hematology, Ministry of Health of the Russian Federation, Moscow, 125167, Russia. loel@mail.ru., Sadovskaya AV; National Medical Research Center for Hematology, Ministry of Health of the Russian Federation, Moscow, 125167, Russia.; Lomonosov Moscow State University, Moscow, 119991, Russia., Sats NV; National Medical Research Center for Hematology, Ministry of Health of the Russian Federation, Moscow, 125167, Russia., Kapranov NM; National Medical Research Center for Hematology, Ministry of Health of the Russian Federation, Moscow, 125167, Russia., Davydova YO; National Medical Research Center for Hematology, Ministry of Health of the Russian Federation, Moscow, 125167, Russia., Fastova EA; National Medical Research Center for Hematology, Ministry of Health of the Russian Federation, Moscow, 125167, Russia., Magomedova AU; National Medical Research Center for Hematology, Ministry of Health of the Russian Federation, Moscow, 125167, Russia., Vasilyeva AN; National Medical Research Center for Hematology, Ministry of Health of the Russian Federation, Moscow, 125167, Russia., Aleshina OA; National Medical Research Center for Hematology, Ministry of Health of the Russian Federation, Moscow, 125167, Russia., Arapidi GP; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, Moscow, 119435, Russia.; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.; Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia., Shender VO; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, Moscow, 119435, Russia.; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia., Smirnov IP; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, Moscow, 119435, Russia., Pobeguts OV; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, Moscow, 119435, Russia., Lagarkova MA; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, Moscow, 119435, Russia., Drize NI; National Medical Research Center for Hematology, Ministry of Health of the Russian Federation, Moscow, 125167, Russia., Parovichnikova EN; National Medical Research Center for Hematology, Ministry of Health of the Russian Federation, Moscow, 125167, Russia. |
| Abstrakt: |
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. |
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