title: Mast cells and eosinophils in mastocytosis, chronic eosinophilic leukemia, and non-clonal disorders.
abstract: Mast cells and eosinophils often travel in the same biologic circles. In non-clonal states, such as allergic and inflammatory conditions, cell-to-cell contact and the pleiotropic actions of multiple cytokines and chemokines, derived from local tissues or mast cells themselves, foster the co-recruitment of these cells to the same geographic cellular niche. While eosinophils and mast cells serve critical roles as part of the host immune response and in maintenance of normal homeostasis, these cell types can undergo neoplastic transformation due to the development of clonal molecular abnormalities that arise in early hematopoietic progenitors. The dysregulated tyrosine kinases, D816V KIT and FIP1L1-PDGFRA, are the prototypic oncogenic lesions resulting in systemic mastocytosis (SM) and chronic eosinophilic leukemia, respectively. We review the pathobiology of these myeloproliferative neoplasms (MPNs) with a focus on the relationship between mast cells and eosinophils, and discuss murine models, which further elucidate how the phenotype of these diseases can be influenced by stem cell factor (SCF) and expression of the potent eosinophilopoietic cytokine, interleukin-5 (IL-5). Therapy of SM and FIP1L1-PDGFRA-positive disease and the prognostic relevance of increased peripheral blood and tissue mast cells in hematolymphoid malignancies will also be addressed.
authors.affiliation: Stanford University School of Medicine/Stanford Cancer Institute, Stanford, CA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Gotlib
authors.forename: Cem
authors.initials: C
authors.lastname: Akin
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D008415:Mastocytosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000276:immunology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000276:immunology; D019089:Stem Cell Factor / Q000276:immunology; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics / Q000276:immunology
chemical_list: C508599:IL5 protein, human; D015848:Interleukin-5; D015514:Oncogene Proteins, Fusion; D019089:Stem Cell Factor; D039221:mRNA Cleavage and Polyadenylation Factors; C479819:FIP1L1-PDGFRA fusion protein, human; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha