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来自JAK2+骨髓增殖性肿瘤的间充质基质细胞(MSC)与正常MSC不同,并有助于维持肿瘤性造血。

Mesenchymal stromal cells (MSC) from JAK2+ myeloproliferative neoplasms differ from normal MSC and contribute to the maintenance of neoplastic hematopoiesis.

作者信息

Ramos Teresa L, Sánchez-Abarca Luis Ignacio, Rosón-Burgo Beatriz, Redondo Alba, Rico Ana, Preciado Silvia, Ortega Rebeca, Rodríguez Concepción, Muntión Sandra, Hernández-Hernández Ángel, De Las Rivas Javier, González Marcos, González Porras José Ramón, Del Cañizo Consuelo, Sánchez-Guijo Fermín

机构信息

Universidad de Salamanca-IBSAL-Hospital Universitario, Servicio de Hematología, Salamanca, Spain.

Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain.

出版信息

PLoS One. 2017 Aug 10;12(8):e0182470. doi: 10.1371/journal.pone.0182470. eCollection 2017.

DOI:10.1371/journal.pone.0182470
PMID:28796790
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5552029/
Abstract

There is evidence of continuous bidirectional cross-talk between malignant cells and bone marrow-derived mesenchymal stromal cells (BM-MSC), which favors the emergence and progression of myeloproliferative neoplastic (MPN) diseases. In the current work we have compared the function and gene expression profile of BM-MSC from healthy donors (HD-MSC) and patients with MPN (JAK2V617F), showing no differences in the morphology, proliferation and differentiation capacity between both groups. However, BM-MSC from MPN expressed higher mean fluorescence intensity (MIF) of CD73, CD44 and CD90, whereas CD105 was lower when compared to controls. Gene expression profile of BM-MSC showed a total of 169 genes that were differentially expressed in BM-MSC from MPN patients compared to HD-MSC. In addition, we studied the ability of BM-MSC to support the growth and survival of hematopoietic stem/progenitor cells (HSPC), showing a significant increase in the number of CFU-GM colonies when MPN-HSPC were co-cultured with MPN-MSC. Furthermore, MPN-MSC showed alteration in the expression of genes associated to the maintenance of hematopoiesis, with an overexpression of SPP1 and NF-kB, and a downregulation of ANGPT1 and THPO. Our results suggest that BM-MSC from JAK2+ patients differ from their normal counterparts and favor the maintenance of malignant clonal hematopoietic cells.

摘要

有证据表明恶性细胞与骨髓来源的间充质基质细胞(BM-MSC)之间存在持续的双向串扰,这有利于骨髓增殖性肿瘤(MPN)疾病的发生和发展。在当前的研究中,我们比较了健康供体的BM-MSC(HD-MSC)和MPN患者(JAK2V617F)的功能和基因表达谱,结果显示两组在形态、增殖和分化能力方面没有差异。然而,与对照组相比,MPN患者的BM-MSC表达的CD73、CD44和CD90的平均荧光强度(MIF)更高,而CD105则更低。BM-MSC的基因表达谱显示,与HD-MSC相比,MPN患者的BM-MSC共有169个基因表达存在差异。此外,我们研究了BM-MSC支持造血干/祖细胞(HSPC)生长和存活的能力,结果显示当MPN-HSPC与MPN-MSC共培养时,CFU-GM集落数量显著增加。此外,MPN-MSC在与造血维持相关的基因表达方面出现改变,SPP1和NF-κB过表达,而ANGPT1和THPO下调。我们的结果表明,JAK2+患者的BM-MSC与其正常对应物不同,有利于恶性克隆造血细胞的维持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/3361184795ff/pone.0182470.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/01dfc0b9ed4a/pone.0182470.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/89214465178b/pone.0182470.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/29eea7b2c8d6/pone.0182470.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/94204ea44368/pone.0182470.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/9e6e9ae5d25d/pone.0182470.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/80055b658f3a/pone.0182470.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/3361184795ff/pone.0182470.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/01dfc0b9ed4a/pone.0182470.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/89214465178b/pone.0182470.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/29eea7b2c8d6/pone.0182470.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/94204ea44368/pone.0182470.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/9e6e9ae5d25d/pone.0182470.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/80055b658f3a/pone.0182470.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8164/5552029/3361184795ff/pone.0182470.g007.jpg

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