title: Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis, and imatinib responsiveness.
abstract: Since serum tryptase levels are elevated in some patients with myeloproliferative disorders, we examined their utility in identifying a subset of patients with hypereosinophilic syndrome (HES) and an underlying myeloproliferative disorder. Elevated serum tryptase levels (> 11.5 ng/mL) were present in 9 of 15 patients with HES and were associated with other markers of myeloproliferation, including elevated B12 levels and splenomegaly. Although bone marrow biopsies in these patients showed increased numbers of CD25+ mast cells and atypical spindle-shaped mast cells, patients with HES and elevated serum tryptase could be distinguished from patients with systemic mastocytosis and eosinophilia by their clinical manifestations, the absence of mast cell aggregates, the lack of a somatic KIT mutation, and the presence of the recently described fusion of the Fip1-like 1 (FIP1L1) gene to the platelet-derived growth factor receptor alpha gene (PDGFRA). Patients with HES and elevated serum tryptase were more likely to develop fibroproliferative end organ damage, and 3 of 9 died within 5 years of diagnosis in contrast to 0 of 6 patients with normal serum tryptase levels. All 6 patients with HES and elevated tryptase treated with imatinib demonstrated a clinical and hematologic response. In summary, elevated serum tryptase appears to be a sensitive marker of a myeloproliferative variant of HES that is characterized by tissue fibrosis, poor prognosis, and imatinib responsiveness.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. aklion@nih.gov
authors.forename: Amy D
authors.initials: AD
authors.lastname: Klion
authors.forename: Pierre
authors.initials: P
authors.lastname: Noel
authors.forename: Cem
authors.initials: C
authors.lastname: Akin
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Law
authors.forename: D Gary
authors.initials: DG
authors.lastname: Gilliland
authors.forename: Jan
authors.initials: J
authors.lastname: Cools
authors.forename: Dean D
authors.initials: DD
authors.lastname: Metcalfe
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D001549:Benzamides; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D002894:Chromosomes, Human, Pair 4; D004719:Endomyocardial Fibrosis / Q000201:enzymology / Q000473:pathology; D004804:Eosinophils / Q000473:pathology; D005260:Female; D005355:Fibrosis; D017353:Gene Deletion; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D000068877:Imatinib Mesylate; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008171:Lung Diseases / Q000201:enzymology; D008297:Male; D008407:Mast Cells / Q000473:pathology; D008415:Mastocytosis / Q000201:enzymology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009196:Myeloproliferative Disorders / Q000201:enzymology*; D015514:Oncogene Proteins, Fusion; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*; D012313:RNA / Q000097:blood; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000097:blood*; D013163:Splenomegaly / Q000201:enzymology; D053802:Tryptases; D014805:Vitamin B 12 / Q000097:blood; D039221:mRNA Cleavage and Polyadenylation Factors / Q000737:chemistry / Q000235:genetics
chemical_list: D001549:Benzamides; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011743:Pyrimidines; D039221:mRNA Cleavage and Polyadenylation Factors; D012313:RNA; D000068877:Imatinib Mesylate; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha; D012697:Serine Endopeptidases; D053802:Tryptases; D014805:Vitamin B 12