title: KIT D816V-associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia are distinct entities.
abstract: BACKGROUND
  The broad and overlapping clinical manifestations of D816V KIT-associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia (CEL), coupled with the increase in activated eosinophils and mast cells seen in both disorders, have led to confusion in the nomenclature. It is of paramount importance, however, to distinguish between these 2 groups of patients because of differences in clinical sequelae, prognoses, and selection of treatment.
  
  
  OBJECTIVE
  We thus sought to identify clinical and laboratory features that could be used to distinguish these 2 diagnoses.
  
  
  METHODS
  We compared 12 patients with D816V-positive systemic mastocytosis with eosinophilia with 17 patients with FIP1L1/PDGFRA-positive CEL. Distinguishing features were used to create a risk factor scoring system.
  
  
  RESULTS
  This system correctly classified 16 of 17 FIP1L1/PDGFRA-positive patients with CEL and all 12 patients with systemic mastocytosis with eosinophilia. Thirty-four FIP1L1/PDGFRA-positive patients described in the literature were also classified using this system, and although a complete set of data was not available for any of the historical patients, 21 were correctly classified.
  
  
  CONCLUSIONS
  These results reinforce the hypothesis that the FIP1L1/PDGFRA gene fusion and D816V-KIT mutation cause distinct clinical syndromes.
  
  
  CONCLUSIONS
  This novel diagnostic approach should prove helpful in clinical practice in the evaluation of patients with increased mast cells and peripheral eosinophilia.
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. marici@mail.nih.gov
authors.forename: Irina
authors.initials: I
authors.lastname: Maric
authors.forename: Jamie
authors.initials: J
authors.lastname: Robyn
authors.forename: Dean D
authors.initials: DD
authors.lastname: Metcalfe
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.forename: Melody
authors.initials: M
authors.lastname: Carter
authors.forename: Todd
authors.initials: T
authors.lastname: Wilson
authors.forename: Weiming
authors.initials: W
authors.lastname: Fu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stoddard
authors.forename: Linda
authors.initials: L
authors.lastname: Scott
authors.forename: Marilyn
authors.initials: M
authors.lastname: Hartsell
authors.forename: Arnold
authors.initials: A
authors.lastname: Kirshenbaum
authors.forename: Cem
authors.initials: C
authors.lastname: Akin
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.forename: Pierre
authors.initials: P
authors.lastname: Noel
authors.forename: Amy D
authors.initials: AD
authors.lastname: Klion
mesh_terms: D004802:Eosinophilia / Q000145:classification* / Q000175:diagnosis / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000175:diagnosis* / Q000503:physiopathology*; D016130:Immunophenotyping; D008297:Male; D034721:Mastocytosis, Systemic / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D012150:Polymorphism, Restriction Fragment Length; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism*
chemical_list: D015514:Oncogene Proteins, Fusion; 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