Sadovskaya Aleksandra, Petinati Nataliya, Shipounova Irina, Drize Nina, Smirnov Igor, Pobeguts Olga, Arapidi Georgiy, Lagarkova Maria, Karaseva Luiza, Pokrovskaya Olga, Kuzmina Larisa, Vasilieva Anastasia, Aleshina Olga, Parovichnikova Elena
National Medical Research Center for Hematology, Moscow 125167, Russia.
Federal State Budget Educational Institution of Higher Education, M.V. Lomonosov Moscow State University, Moscow 119991, Russia.
Int J Mol Sci. 2024 Dec 11;25(24):13285. doi: 10.3390/ijms252413285.
In patients with acute leukemia (AL), malignant cells and therapy modify the properties of multipotent mesenchymal stromal cells (MSCs) and their descendants, reducing their ability to maintain normal hematopoiesis. The aim of this work was to elucidate the alterations in MSCs at the onset and after therapy in patients with AL. The study included MSCs obtained from the bone marrow of 78 AL patients (42 AML and 36 ALL) and healthy donors. MSC growth characteristics, gene expression pattern, proteome and secretome were studied using appropriate methods. The concentration of MSCs in the bone marrow, proliferative potential, the expression of several genes, proteomes and secretomes were altered in AL-MSCs. Stromal progenitors had been affected differently in ALL and AML patients. In remission, MSC functions remain impaired despite the absence of tumor cells and the maintenance of benign hematopoietic cells. AL causes crucial and, to a large extent, irreversible changes in bone marrow MSCs.
在急性白血病(AL)患者中,恶性细胞和治疗会改变多能间充质基质细胞(MSC)及其后代的特性,降低它们维持正常造血的能力。这项研究的目的是阐明AL患者发病时及治疗后MSC的变化。该研究纳入了从78例AL患者(42例急性髓系白血病和36例急性淋巴细胞白血病)以及健康供体的骨髓中获取的MSC。使用适当的方法研究了MSC的生长特性、基因表达模式、蛋白质组和分泌组。AL-MSC中骨髓MSC的浓度、增殖潜能、几个基因的表达、蛋白质组和分泌组均发生了改变。基质祖细胞在急性淋巴细胞白血病和急性髓系白血病患者中受到的影响有所不同。在缓解期,尽管没有肿瘤细胞且良性造血细胞得以维持,但MSC的功能仍然受损。AL会导致骨髓MSC发生关键且在很大程度上不可逆的变化。