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

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

Author information

1
Universidad de Salamanca-IBSAL-Hospital Universitario, Servicio de Hematología, Salamanca, Spain.
2
Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain.
3
Centro de Investigación del Cáncer, Universidad de Salamanca y Consejo Superior de Investigaciones Científicas (IBMCC, USAL/CSIC), Salamanca, Spain.
4
Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Salamanca, Spain.
5
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.

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.

PMID:
28796790
PMCID:
PMC5552029
DOI:
10.1371/journal.pone.0182470
[Indexed for MEDLINE]
Free PMC Article

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