title: Cell(s) of Origin of Langerhans Cell Histiocytosis.
abstract: Langerhans cell histiocytosis (LCH) is heterogeneous disease characterized by common histology of inflammatory lesions containing Langerin(+) (CD207) histiocytes. Emerging data support a model in which MAPK activation in self-renewing hematopoietic progenitors may drive disseminated high-risk disease, whereas MAPK activation in more differentiated committed myeloid populations may induce low-risk LCH. The heterogeneous clinical manifestations with shared histology may represent the final common pathway of an acquired defect of differentiation, initiated at more than one point. Implications of this model include re-definition of LCH as a myeloid neoplasia and re-focusing therapeutic strategies on the cells and lineages of origin.
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Collin
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Venetia
authors.initials: V
authors.lastname: Bigley
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: McClain
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: ceallen@txch.org.
authors.forename: Carl E
authors.initials: CE
authors.lastname: Allen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology; D006646:Histiocytosis, Langerhans-Cell / Q000175:diagnosis* / Q000209:etiology*; D006801:Humans
keywords: BRAF; Dendritic cell; Langerhans cell histiocytosis; MAPK signaling; Myeloid differentiation