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

[EN]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 expr...

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Detalles Bibliográficos
Autores: Ramos, Teresa L., Sánchez Abarca, Luis Ignacio, Rosón Burgo, Beatriz, Redondo Guijo, Alba María, Rico, Ana, Preciado Pérez, Silvia, Ortega, Rebeca, Rodríguez, Concepción, Muntión Olave, María Sandra, Hernández Hernández, Ángel, Rivas Sanz, Javier de las, González, Marcos, González Porras, José Ramón, Cañizo Fernández-Roldán, María Consuelo del, Sánchez-Guijo Martín, Fermín
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/135282
Acceso en línea:http://hdl.handle.net/10366/135282
https://doi.org/10.1371/journal.pone.0182470
Access Level:acceso abierto
Palabra clave:Mesenchymal stromal cells
Cell biology
Neoplastic hematopoiesis
Células madre
Neoplasias hematopoyeticas
Descripción
Sumario:[EN]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 (HDMSC) 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

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