| Autor: |
Sadovskaya A; National Medical Research Center for Hematology, 125167 Moscow, Russia.; Department of Immunology, Faculty of Biology, Federal State Budget Educational Institution of Higher Education M.V. Lomonosov Moscow State University, 119991 Moscow, Russia., Petinati N; National Medical Research Center for Hematology, 125167 Moscow, Russia., Drize N; National Medical Research Center for Hematology, 125167 Moscow, Russia., Smirnov I; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia., Pobeguts O; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia., Arapidi G; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia.; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia., Lagarkova M; Department of Immunology, Faculty of Biology, Federal State Budget Educational Institution of Higher Education M.V. Lomonosov Moscow State University, 119991 Moscow, Russia.; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia., Belyavsky A; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Vasilieva A; National Medical Research Center for Hematology, 125167 Moscow, Russia., Aleshina O; National Medical Research Center for Hematology, 125167 Moscow, Russia., Parovichnikova E; National Medical Research Center for Hematology, 125167 Moscow, Russia. |
| Abstrakt: |
In patients with acute myeloid leukemia (AML), malignant cells modify the properties of multipotent mesenchymal stromal cells (MSCs), reducing their ability to maintain normal hematopoiesis. The aim of this work was to elucidate the role of MSCs in supporting leukemia cells and the restoration of normal hematopoiesis by analyzing ex vivo MSC secretomes at the onset of AML and in remission. The study included MSCs obtained from the bone marrow of 13 AML patients and 21 healthy donors. The analysis of proteins contained in the MSCs-conditioned medium demonstrated that secretomes of patient MSCs differed little between the onset of AML and remission; pronounced differences were observed between MSC secretomes of AML patients and healthy donors. The onset of AML was accompanied by a decrease in the secretion of proteins related to ossification, transport, and immune response. In remission, but not at the onset, secretion of proteins responsible for cell adhesion, immune response, and complement was reduced compared to donors. We conclude that AML causes crucial and, to a large extent, irreversible changes in the secretome of bone marrow MSCs ex vivo. In remission, functions of MSCs remain impaired despite the absence of tumor cells and the formation of benign hematopoietic cells. |
