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.
Copyright © 2017 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
Publication types
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Review
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Marrow / drug effects
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Bone Marrow / metabolism
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Bone Marrow / pathology
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Bone Marrow Cells / drug effects*
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Bone Marrow Cells / metabolism
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Bone Marrow Cells / pathology
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Cell Proliferation
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Disease Models, Animal
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Gene Expression
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Humans
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Mice
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Mice, Transgenic
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Molecular Targeted Therapy*
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Platelet Factor 4 / genetics*
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Platelet Factor 4 / metabolism
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Primary Myelofibrosis / drug therapy*
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Primary Myelofibrosis / genetics
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Primary Myelofibrosis / metabolism
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Primary Myelofibrosis / pathology
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Pyridines / pharmacology*
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Pyrimidines / pharmacology*
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Zinc Finger Protein GLI1 / antagonists & inhibitors
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Zinc Finger Protein GLI1 / genetics*
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Zinc Finger Protein GLI1 / metabolism
Substances
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GANT 61
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GLI1 protein, human
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Pyridines
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Pyrimidines
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Zinc Finger Protein GLI1
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Platelet Factor 4