ABSTRACT
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.
Subject(s)
Leukemia, Myeloid, Acute , Mesenchymal Stem Cells , Humans , Leukemia, Myeloid, Acute/metabolism , Bone Marrow/metabolism , Mesenchymal Stem Cells/metabolism , Hematopoiesis , Stromal Cells/pathology , Bone Marrow Cells/metabolism , Tumor MicroenvironmentABSTRACT
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.
