title: Multilineage involvement of the fusion gene in patients with FIP1L1/PDGFRA-positive hypereosinophilic syndrome.
abstract: Myeloproliferative hypereosinophilic syndrome (MHES) is a disorder characterised by male predominance, marked eosinophilia, splenomegaly, tissue fibrosis, elevated serum tryptase and the presence of the FIP1L1/PDGFRA fusion gene in peripheral blood mononuclear cells. The characteristic hypercellular bone marrow with dysplastic eosinophils and spindle-shaped mast cells suggest that multiple lineages may be involved in the clonal process. To determine which haematopoietic lineages are involved in MHES, we purified cells of specific lineages from patients with MHES and used nested reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR and fluorescence in situ hybridisation to analyse the purified cell populations for the presence of the fusion gene. The fusion gene was detected in eosinophils, neutrophils, mast cells, T cells, B cells and monocytes. These results suggest that the mutation arises in a pluripotential haematopoietic progenitor cell capable of giving rise to multiple lineages. The basis for the preferential expansion of eosinophils and mast cells remains unclear.
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1881, USA. jrobyn@niaid.nih.gov
authors.forename: Jamie
authors.initials: J
authors.lastname: Robyn
authors.forename: Steven
authors.initials: S
authors.lastname: Lemery
authors.forename: J Philip
authors.initials: JP
authors.lastname: McCoy
authors.forename: Joseph
authors.initials: J
authors.lastname: Kubofcik
authors.forename: Yae-Jean
authors.initials: YJ
authors.lastname: Kim
authors.forename: Svetlana
authors.initials: S
authors.lastname: Pack
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.forename: Cynthia
authors.initials: C
authors.lastname: Dunbar
authors.forename: Amy D
authors.initials: AD
authors.lastname: Klion
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology / Q000502:physiology; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000235:genetics* / Q000276:immunology; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000502:physiology; D009000:Monocytes / Q000276:immunology / Q000502:physiology; D009504:Neutrophils / Q000276:immunology / Q000502:physiology; D015514:Oncogene Proteins, Fusion / Q000032:analysis*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D039221:mRNA Cleavage and Polyadenylation Factors / Q000032:analysis*
chemical_list: D015703:Antigens, CD; D015514:Oncogene Proteins, Fusion; D039221:mRNA Cleavage and Polyadenylation Factors; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha