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

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

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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Cycle
  • Cell Line, Tumor
  • Coculture Techniques
  • Female
  • Gene Expression
  • Hematologic Neoplasms / blood
  • Hematologic Neoplasms / enzymology
  • Hematologic Neoplasms / pathology*
  • Hematopoiesis
  • Humans
  • Janus Kinase 2 / metabolism*
  • Male
  • Mesenchymal Stem Cells / physiology*
  • Middle Aged

Substances

  • Biomarkers, Tumor
  • JAK2 protein, human
  • Janus Kinase 2

Grants and funding

Teresa Lopes Ramos is supported by a fellowship by the Portuguese Fundação para a Ciência e Tecnologia (SFRH/BD/86451/2012). Sandra Muntion is supported by Red TerCel from Instituto de Salud Carlos III (RD12/0019/0017). Silvia Preciado is supported by a Universidad de Salamanca-Banco de Santander joint grant. This study was partially supported by grant GRS 1034/A/14 and BIO/SA28/14 from Consejería de Sanidad de la Junta de Castilla y León.