The spleen of patients with myelofibrosis harbors defective mesenchymal stromal cells

Am J Hematol. 2018 May;93(5):615-622. doi: 10.1002/ajh.25047. Epub 2018 Feb 8.


Splenic hematopoiesis is a major feature in the course of myelofibrosis (MF). In fact, the spleen of patients with MF contains malignant hematopoietic stem cells retaining a complete differentiation program, suggesting both a pivotal role of the spleen in maintaining the disease and a tight regulation of hematopoiesis by the splenic microenvironment, in particular by mesenchymal stromal cells (MSCs). Little is known about splenic MSCs (Sp-MSCs), both in normal and in pathological context. In this work, we have in vitro expanded and characterized Sp-MSCs from 25 patients with MF and 13 healthy subjects (HS). They shared similar phenotype, growth kinetics, and differentiation capacity. However, MF Sp-MSCs expressed significant lower levels of nestin, and favored megakaryocyte (Mk) differentiation in vitro at a larger extent than their normal counterpart. Moreover, they showed a significant upregulation of matrix metalloprotease 2 (MMP2) and fibronectin 1 (FN1) genes both at mRNA expression and at protein level, and, finally, developed genetic abnormalities which were never detected in HS-derived Sp-MSCs. Our data point toward the existence of a defective splenic niche in patients with MF that could be responsible of some pathological features of the disease, including the increased trafficking of CD34+ cells and the expansion of the megakaryocytic lineage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD34
  • Case-Control Studies
  • Cell Movement
  • Cell Proliferation
  • Female
  • Fibronectins / metabolism
  • Hematopoiesis
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Megakaryocytes / pathology
  • Mesenchymal Stem Cells / pathology*
  • Middle Aged
  • Nestin / metabolism
  • Primary Myelofibrosis / pathology*
  • Spleen / pathology*
  • Young Adult


  • Antigens, CD34
  • FN1 protein, human
  • Fibronectins
  • Nestin
  • MMP2 protein, human
  • Matrix Metalloproteinase 2