Primary myelofibrosis marrow-derived CD14+/CD34- monocytes induce myelofibrosis-like phenotype in immunodeficient mice and give rise to megakaryocytes

PLoS One. 2019 Sep 30;14(9):e0222912. doi: 10.1371/journal.pone.0222912. eCollection 2019.

Abstract

To confirm that neoplastic monocyte-derived collagen- and fibronectin-producing fibrocytes induce bone marrow (BM) fibrosis in primary myelofibrosis (PMF), we injected PMF BM-derived fibrocyte-precursor CD14+/CD34- monocytes into the tail vein of NOD-SCID-γ (NSG) mice. PMF BM-derived CD14+/CD34- monocytes engrafted and induced a PMF-like phenotype with splenomegaly, myeloid hyperplasia with clusters of atypical megakaryocytes, persistence of the JAK2V617F mutation, and BM and spleen fibrosis. As control we used normal human BM-derived CD14+/CD34- monocytes. These monocytes also engrafted and gave rise to normal megakaryocytes that, like PMF CD14+/CD34--derived megakaryocytes, expressed HLA-ABC and human CD42b antigens. Using 2 clonogenic assays we confirmed that PMF and normal BM-derived CD14+/CD34- monocytes give rise to megakaryocyte colony-forming cells, suggesting that a subpopulation BM monocytes harbors megakaryocyte progenitor capacity. Taken together, our data suggest that PMF monocytes induce myelofibrosis-like phenotype in immunodeficient mice and that PMF and normal BM-derived CD14+/CD34- monocytes give rise to megakaryocyte progenitor cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, CD34 / genetics
  • Antigens, CD34 / immunology
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / pathology
  • Female
  • Fibroblasts / immunology*
  • Fibroblasts / pathology
  • Fibroblasts / transplantation
  • Gene Expression
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Humans
  • Hyperplasia / etiology
  • Hyperplasia / genetics
  • Hyperplasia / immunology*
  • Hyperplasia / pathology
  • Immunocompromised Host*
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / immunology
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / immunology
  • Megakaryocytes / immunology
  • Megakaryocytes / pathology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Monocytes / immunology*
  • Monocytes / pathology
  • Monocytes / transplantation
  • Mutation
  • Primary Myelofibrosis / etiology
  • Primary Myelofibrosis / genetics
  • Primary Myelofibrosis / immunology*
  • Primary Myelofibrosis / pathology
  • Splenomegaly / etiology
  • Splenomegaly / genetics
  • Splenomegaly / immunology*
  • Splenomegaly / pathology

Substances

  • Antigens, CD34
  • Cd14 protein, mouse
  • HLA Antigens
  • Lipopolysaccharide Receptors
  • Jak2 protein, mouse
  • Janus Kinase 2