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Title

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

AuthorsRamos, Teresa L.; Sánchez-Abarca, Luis Ignacio; Rosón, Beatriz ; Redondo, Alba; Rico, Ana; Preciado, Silvia; Ortega, Rebeca ; Rodríguez, Concepción; Muntión, Sandra; Hernández-Hernández, Angel; De Las Rivas, Javier ; González, Marcos ; González-Porras, José R.; Cañizo, María Consuelo del; Sánchez-Guijo, Fermín M.
Issue Date2017
PublisherPublic Library of Science
CitationPLoS ONE 12(8): e0182470 (2017)
AbstractThere 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.
Publisher version (URL)https://doi.org/10.1371/journal.pone.0182470
URIhttp://hdl.handle.net/10261/169101
Identifiersdoi: 10.1371/journal.pone.0182470
e-issn: 1932-6203
Appears in Collections:(IBMCC) Artículos
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