Analysis of Bone Tissue Condition in Patients with Diffuse Large B-Cell Lymphoma without Bone Marrow Involvement
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Bulletin of Experimental Biology and Medicine, Vol. 169, No. 5, September, 2020
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ONCOLOGY Analysis of Bone Tissue Condition in Patients with Diffuse Large B-Cell Lymphoma without Bone Marrow Involvement E. A. Fastova, A. U. Magomedova, S. K. Kravchenko, N. A. Petinati, N. V. Sats, N. I. Drize, and V. G. Savchenko
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 5, pp. 608-613, May, 2020 Original article submitted December 6, 2019 We studied changes in the bone tissue in patients with diffuse large B-cell lymphoma at the onset of the disease (N=41; before chemotherapy) and 5-16 years after the end of treatment (N=47). Osteodensitometry, biochemical markers of osteoporosis in the blood and urine, and gene expression in multipotent mesenchymal stromal cells were analyzed. In multipotent mesenchymal stromal cells of all patients, the expression of genes associated with bone and cartilage differentiation (FGF2, FGFR1, FGFR2, BGLAP, SPP1, TGFB1, and SOX9) was changed. In primary patients, the ratio of deoxypyridinoline/creatinine in the urine and blood level of β-cross-laps were increased, while plasma concentration of vitamin D was reduced, which indicates activation of bone resorption. No differences between the groups were revealed by osteodensitometry. No direct relationship between changes in gene expression in multipotent mesenchymal stromal cells and osteoporosis markers was found. The presence of a tumor in the body affects the bone marrow stroma, but achievement of remission and compensatory mechanisms provide age-appropriate condition of the bone tissue. Key Words: diffuse large B-cell lymphoma; multipotent mesenchymal stromal cells; bone mineral density; markers of bone metabolism; gene expression The bone marrow harbors two types of stem cells: hemopoietic and stromal. Mesenchymal stem cells are the precursors of all lines of differentiation of the bone marrow stroma regulating hemopoiesis. Multipotent mesenchymal stromal cells (MMSC) are descendants of a stem cell identified in culture; these plastic-adherent cells can differentiate into osteogenic, chondrogenic, and adipogenic lineage cells [4]. MMSC are involved in the formation and remodeling of the bone tissue. In 10-25% patients with diffuse large B-cell lymphoma (DLBCL), bone marrow involvement is detected using histological or molecular methods [11]. In National Medical Research Center of Hematology, Ministry of Health of the Russian Federation, Moscow, Russia. Address for correspondence: [email protected]. E. A. Fastova
the remaining patients with DLBCL, the bone marrow is believed to be not involved in the tumor process. It could be assumed that stromal bone marrow precursor cells in this group of patients are unchanged, because the direct influence of tumor cells is excluded. It is known that tumor cells adapt the bone marrow stromal microenvironment in leukemia. The effect of tumor cells can be directly transmitted by the paracrine route or through exosomes secreted by tumor cells [7]. However, previous stu
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