RESUMEN
In acute leukemia, the stromal microenvironment of the bone marrow that regulates hematopoiesis is modified under the influence of malignant cells. Chemotherapy also adversely affects stromal cells. Multipotent mesenchymal stromal cells (MSC) are involved in the formation of the stromal microenvironment and in the regulation of normal and tumor hematopoietic cells. The properties of MSC from the bone marrow of patients with acute myeloid and lymphoid leukemia were studied at the onset of the disease and after achieving remission. The immunophenotype and the level of gene expression were analyzed in MSC of 34 patients. In MSC from patients with acute leukemia, the expression of CD105 and CD274 was significantly reduced in comparison with MSC from healthy donors. At the onset of the disease, the expression of IL6, JAG1, PPARG, IGF1, and PDGFRA was enhanced, while the expression of IL1B, IL8, SOX9, ANG1, and TGFB was reduced. All these changes affect the course of the disease in patients and can be the targets of therapeutic intervention.
Asunto(s)
Leucemia Mieloide Aguda , Células Madre Mesenquimatosas , Humanos , Leucemia Mieloide Aguda/metabolismo , Médula Ósea/metabolismo , Células Madre Mesenquimatosas/metabolismo , Hematopoyesis , Células del Estroma/patología , Células de la Médula Ósea/metabolismo , Microambiente TumoralRESUMEN
In patients with acute leukemia, not only normal hematopoiesis, but also bone marrow stromal microenvironment is damaged. Multipotent mesenchymal stromal cells (MSC) are essential for the formation and function of the stromal microenvironment. Analysis of changes in MSC is important for the development of new approaches to leukemia therapy. The metabolism of mitochondria in MSC, relative content of mitochondrial DNA, and expression levels of genes encoding PGC-1α and Nrf2 proteins, important regulators of biogenesis, were studied using real-time PCR. Relative content of mitochondrial DNA does not change in MSC of acute leukemia patients at the onset of disease or in remission. Relative expression level of the gene encoding PGC-1α protein in MSC does not change significantly. However, relative expression level of the gene encoding Nrf2, an important antioxidant activity regulator, insignificantly decreases in patients at the onset of acute leukemia, and this decrease becomes significant upon reaching remission.
Asunto(s)
Leucemia Mieloide Aguda , Células Madre Mesenquimatosas , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Mitocondrias/genética , Mitocondrias/metabolismo , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Células Madre Mesenquimatosas/metabolismo , Microambiente TumoralRESUMEN
The objects of researches are the soil and wild vegetation in the region of the radioactive waste storage situation. In result of monitoring it was recognized 137Cs unlike 90Sr did not spread out of storage territory in spite of trench destruction and migration of radionuclides with surface and ground waters. The forms of 137Cs, 90Sr and natural radionuclide 226Ra in soils and coefficients of 90Sr accumulation for the different kinds of plants growing at the territory of storage and 50-m zone around it were researched. The low specific activities of mobile forms of 90Sr were recognized for samples of soils selected from lowland by the terrace. The considerable differences were found for specific activities of radionuclides for different soil layers. Essential irregularity of soil surface and vegetation contamination at the test points disposed at a short distances from each other also was found. The interpretation of obtained results is presented.