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Oncogene-Induced Senescence as a New Mechanism of Disease: The Paradigm of Erdheimâ€'Chester Disease
- Source :
- Frontiers in Immunology, Vol 5 (2014), Frontiers in Immunology
- Publication Year :
- 2014
- Publisher :
- Frontiers Media SA, 2014.
-
Abstract
- Erdheim-Chester disease (ECD) is a rare form of systemic histiocytosis characterized by the diffuse infiltration of tissues by lipid-laden macrophages. As the clinical course and prognosis are highly influenced by site of disease involvement, ECD course ranges from asymptomatic to life threatening, with a reported global 5-year mortality of 30-40%. Whether ECD is an inflammatory or clonal disease in its nature has long been debated. The disease is characterized by a network of pro-inflammatory cyto/chemokines responsible for the recruitment and activation of histiocytes into ECD lesions, similarly to what reported in Langerhans cell histiocytosis (LCH). Growing evidence supports a central role of the oncogenic BRAF(V600E) mutation in histiocytosis pathogenesis, and suggests oncogene-induced senescence (OIS), a major protective mechanism against oncogenic events characterized by cell-cycle arrest and the induction of pro-inflammatory molecules, as the possible link between the oncogenic mutation and the observed inflammation. Indeed, ECD recapitulates in vivo the molecular events associated with OIS, i.e., cell-cycle arrest and a potent local inflammatory response. Accordingly, the infiltration of different tissues by macrophages and the inflammatory local and systemic effects observed in ECD likely represent a drawback of OIS. Therefore, these findings delineate a new conception of OIS as a new pathogenic mechanism intrinsically responsible for disease development.
- Subjects :
- lcsh:Immunologic diseases. Allergy
Senescence
Erdheim-Chester Disease
genetic structures
Mini Review
Erdheim–Chester disease
Immunology
Inflammation
Disease
BRAF kinases
Pathogenesis
Langerhans cell histiocytosis
Immunology and Allergy
Medicine
Histiocyte
business.industry
Macrophages
oncogene-induced senescence
medicine.disease
Histiocytosis
medicine.symptom
lcsh:RC581-607
business
Subjects
Details
- ISSN :
- 16643224
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....0cd1d8f8f534ea9e8e478b6d4ef3736a