title: Targeted next-generation sequencing identifies a subset of idiopathic hypereosinophilic syndrome with features similar to chronic eosinophilic leukemia, not otherwise specified.
abstract: The distinction between chronic eosinophilic leukemia, not otherwise specified and idiopathic hypereosinophilic syndrome largely relies on clonality assessment. Prior to the advent of next-generation sequencing, clonality was usually determined by cytogenetic analysis. We applied targeted next-generation sequencing panels designed for myeloid neoplasms to bone marrow specimens from a cohort of idiopathic hypereosinophilic syndrome patients (n=51), and assessed the significance of mutations in conjunction with clinicopathological features. The findings were further compared with those of 17 chronic eosinophilic leukemia, not otherwise specified patients defined by their abnormal cytogenetics and/or increased blasts. Mutations were detected in 14/51 idiopathic hypereosinophilic syndrome patients (idiopathic hypereosinophilic syndrome/next-generation sequencing-positive) (28%), involving single gene in 7 and ≥2 in 7 patients. The more frequently mutated genes included ASXL1 (43%), TET2 (36%), EZH2 (29%), SETBP1 (22%), CBL (14%), and NOTCH1 (14%). Idiopathic hypereosinophilic syndrome/next-generation sequencing-positive patients showed a number of clinical features and bone marrow findings resembling chronic eosinophilic leukemia, not otherwise specified. Chronic eosinophilic leukemia, not otherwise specified patients showed a disease-specific survival of 14.4 months, markedly inferior to idiopathic hypereosinophilic syndrome/next-generation sequencing-negative (P<0.001), but not significantly different from idiopathic hypereosinophilic syndrome/next-generation sequencing-positive (P=0.117). These data suggest that targeted next-generation sequencing helps to establish clonality in a subset of patients with hypereosinophilia that would otherwise be classified as idiopathic hypereosinophilic syndrome. In conjunction with other diagnostic features, mutation data can be used to establish a diagnosis of chronic eosinophilic leukemia, not otherwise specified in patients presenting with hypereosinophilia.
authors.affiliation: Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sa A
authors.initials: SA
authors.lastname: Wang
authors.affiliation: Department of Pathology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Tam
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Albert G
authors.initials: AG
authors.lastname: Tsai
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Arber
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hasserjian
authors.affiliation: Department of Pathology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Julia T
authors.initials: JT
authors.lastname: Geyer
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Tracy I
authors.initials: TI
authors.lastname: George
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Czuchlewski
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Foucar
authors.affiliation: Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Heesun J
authors.initials: HJ
authors.lastname: Rogers
authors.affiliation: Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Bryan Rea
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Bagg
authors.affiliation: Department of Pathology, Brigham and Women Hospital, Boston, MA, USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Dal Cin
authors.affiliation: Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Todd W
authors.initials: TW
authors.lastname: Kelley
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.affiliation: Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueso-Ramos
authors.affiliation: Department of Pathology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001856:Bone Marrow Examination; D004252:DNA Mutational Analysis / Q000379:methods*; D003937:Diagnosis, Differential; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D059785:Karyotype; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D014481:United States; D055815:Young Adult
chemical_list: D005819:Genetic Markers