Identity of Gli1+ cells in the bone marrow

Exp Hematol. 2017 Oct:54:12-16. doi: 10.1016/j.exphem.2017.06.349. Epub 2017 Jul 6.

Abstract

Bone marrow fibrosis is a critical component of primary myelofibrosis in which normal bone marrow tissue and blood-forming cells are gradually replaced with scar tissue. The specific cellular and molecular mechanisms that cause bone marrow fibrosis are not understood. A recent study using state-of-the-art techniques, including in vivo lineage tracing, provides evidence that Gli1+ cells are the cells responsible for fibrotic disease in the bone marrow. Strikingly, genetic depletion of Gli1+ cells rescues bone marrow failure and abolishes myelofibrosis. This work introduces a new central cellular target for bone marrow fibrosis. The knowledge that emerges from this research will be important for the treatment of several malignant and nonmalignant disorders.

Publication types

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

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Cell Proliferation
  • Disease Models, Animal
  • Gene Expression
  • Humans
  • Mice
  • Mice, Transgenic
  • Molecular Targeted Therapy*
  • Platelet Factor 4 / genetics*
  • Platelet Factor 4 / metabolism
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / genetics
  • Primary Myelofibrosis / metabolism
  • Primary Myelofibrosis / pathology
  • Pyridines / pharmacology*
  • Pyrimidines / pharmacology*
  • Zinc Finger Protein GLI1 / antagonists & inhibitors
  • Zinc Finger Protein GLI1 / genetics*
  • Zinc Finger Protein GLI1 / metabolism

Substances

  • GANT 61
  • GLI1 protein, human
  • Pyridines
  • Pyrimidines
  • Zinc Finger Protein GLI1
  • Platelet Factor 4