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成年急性髓系白血病和急性淋巴细胞白血病患者在异基因造血干细胞移植前后骨髓基质微环境的改变

Alterations of the bone marrow stromal microenvironment in adult patients with acute myeloid and lymphoblastic leukemias before and after allogeneic hematopoietic stem cell transplantation.

作者信息

Shipounova Irina N, Petinati Nataliya A, Bigildeev Alexey E, Drize Nina J, Sorokina Tamara V, Kuzmina Larisa A, Parovichnikova Elena N, Savchenko Valeri G

机构信息

a Physiology of Hematopoiesis Lab , Federal Government Budget Institution National Research Center for Hematology, Ministry of Health , Moscow , Russian Federation.

b Department of High-Dose Chemotherapy , Depressions of Hematopoiesis and Bone Marrow Transplantation, Federal Government Budget Institution National Research Center for Hematology, Ministry of Health , Moscow , Russian Federation.

出版信息

Leuk Lymphoma. 2017 Feb;58(2):408-417. doi: 10.1080/10428194.2016.1187277. Epub 2016 May 31.

Abstract

Bone marrow (BM) derived adult multipotent mesenchymal stromal cells (MMSCs) and fibroblast colony-forming units (CFU-Fs) of 20 patients with acute myeloid leukemia (AML) and 15 patients with acute lymphoblastic leukemia (ALL) before and during 1 year after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) were studied. The growth characteristics of MMSCs of all patients before allo-HSCT were not altered; however, relative expression level (REL) of some genes in MMSCs, but not in CFU-Fs, from AML and ALL patients significantly changed. After allo-HSCT, CFU-F concentration and MMSC production were significantly decreased for 1 year; REL of several genes in MMSCs and CFU-F-derived colonies were also significantly downregulated. Thus, chemotherapy that was used for induction of remission did not impair the function of stromal precursors, but gene expression levels were altered. Allo-HSCT conditioning regimens significantly damaged MMSCs and CFU-Fs, and the effect lasted for at least 1 year.

摘要

对20例急性髓系白血病(AML)患者和15例急性淋巴细胞白血病(ALL)患者在接受异基因造血干细胞移植(allo-HSCT)之前及之后1年内的骨髓(BM)来源的成人多能间充质基质细胞(MMSC)和成纤维细胞集落形成单位(CFU-F)进行了研究。所有患者在allo-HSCT之前MMSC的生长特性未改变;然而,AML和ALL患者MMSC中一些基因的相对表达水平(REL)发生了显著变化,而CFU-F中则未改变。allo-HSCT后,CFU-F浓度和MMSC产量在1年内显著降低;MMSC和CFU-F衍生集落中几个基因的REL也显著下调。因此,用于诱导缓解的化疗并未损害基质前体细胞的功能,但基因表达水平发生了改变。allo-HSCT预处理方案显著损害了MMSC和CFU-F,且这种影响持续了至少1年。

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