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	Amy D Klion, Pierre Noel, Cem Akin, Melissa A Law, D Gary Gilliland, Jan Cools, Dean D Metcalfe, Thomas B Nutman
Journal	Blood (Blood) Vol. 101 Issue 12 Pg. 4660-6 (Jun 15 2003) ISSN: 0006-4971 [Print] United States
PMID	12676775 (Publication Type: Journal Article)
Chemical References	Benzamides Oncogene Proteins, Fusion Piperazines Pyrimidines mRNA Cleavage and Polyadenylation Factors RNA Imatinib Mesylate FIP1L1-PDGFRA fusion protein, human Receptor, Platelet-Derived Growth Factor alpha Serine Endopeptidases Tryptases Vitamin B 12
Topics	Adolescent Adult Aged Amino Acid Sequence Base Sequence Benzamides Biopsy Bone Marrow (pathology) Chromosomes, Human, Pair 4 Endomyocardial Fibrosis (enzymology, pathology) Eosinophils (pathology) Female Fibrosis Gene Deletion Humans Hypereosinophilic Syndrome (drug therapy, enzymology, pathology) Imatinib Mesylate Leukocytes, Mononuclear (enzymology) Lung Diseases (enzymology) Male Mast Cells (pathology) Mastocytosis (enzymology) Middle Aged Molecular Sequence Data Myeloproliferative Disorders (enzymology) Oncogene Proteins, Fusion Piperazines (therapeutic use) Prognosis Pyrimidines (therapeutic use) RNA (blood) Receptor, Platelet-Derived Growth Factor alpha (chemistry, genetics) Reverse Transcriptase Polymerase Chain Reaction Serine Endopeptidases (blood) Splenomegaly (enzymology) Tryptases Vitamin B 12 (blood) mRNA Cleavage and Polyadenylation Factors (chemistry, genetics)

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