淋巴肿瘤中骨髓多能间质基质细胞免疫学特征的分子变化

IF 2.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Nataliya A. Petinati, Aleksandra V. Sadovskaya, Natalia V. Sats, Nikolai M. Kapranov, Yulia O. Davydova, Ekaterina A. Fastova, Aminat U. Magomedova, Anastasia N. Vasilyeva, Olga A. Aleshina, Georgiy P. Arapidi, Viktoria O. Shender, Igor P. Smirnov, Olga V. Pobeguts, Maria A. Lagarkova, Nina I. Drize, Elena N. Parovichnikova
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引用次数: 0

摘要

摘要 免疫系统和骨髓基质细胞在维持正常造血过程中发挥着重要作用。淋巴肿瘤不仅干扰了免疫细胞的发育,还干扰了其他免疫反应机制。骨髓多能间充质基质细胞(MSCs)通过细胞间相互作用和分泌各种细胞因子参与免疫反应调节。在血液恶性肿瘤中,包括间充质干细胞在内的骨髓基质微环境发生了改变。本研究旨在描述急性淋巴细胞白血病(ALL)和弥漫大B细胞淋巴瘤(DLBCL)患者间充质干细胞免疫功能的差异。急性淋巴细胞白血病的恶性细胞来自骨髓中的早期前体细胞,而弥漫性大B细胞淋巴瘤的恶性细胞来自分化程度较高的B细胞。在这项研究中,只纳入了没有骨髓受累的 DLBCL 患者。研究了ALL和DLBCL患者骨髓间充质干细胞在发病和缓解期的生长参数、表面标志物表达、相关基因表达和分泌模式。相应年龄健康供体的间充质干细胞作为对照。研究结果表明,ALL 患者骨髓中间叶干细胞的浓度在发病时会降低,在病情缓解时会恢复;而在 DLBCL 患者中,这一参数没有变化。ALL患者间充质干细胞的增殖能力没有变化;但DLBCL患者的细胞在发病和缓解期的增殖速度明显快于供体。患者间充质干细胞与健康供体间充质干细胞的膜表面标志物表达以及分化、免疫状态维持和细胞因子分泌等重要基因的表达存在明显差异,并取决于疾病的命名。间充质干细胞的分泌物组差异很大;在患者细胞的分泌物组中,一些与免疫反应调节、分化和造血干细胞维持有关的蛋白质被消耗殆尽。淋巴肿瘤导致间充质干细胞的功能免疫状态发生巨大变化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Molecular Changes in Immunological Characteristics of Bone Marrow Multipotent Mesenchymal Stromal Cells in Lymphoid Neoplasia

Molecular Changes in Immunological Characteristics of Bone Marrow Multipotent Mesenchymal Stromal Cells in Lymphoid Neoplasia

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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来源期刊
Biochemistry (Moscow)
Biochemistry (Moscow) 生物-生化与分子生物学
CiteScore
4.70
自引率
3.60%
发文量
139
审稿时长
2 months
期刊介绍: Biochemistry (Moscow) is the journal that includes research papers in all fields of biochemistry as well as biochemical aspects of molecular biology, bioorganic chemistry, microbiology, immunology, physiology, and biomedical sciences. Coverage also extends to new experimental methods in biochemistry, theoretical contributions of biochemical importance, reviews of contemporary biochemical topics, and mini-reviews (News in Biochemistry).
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