title: Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics.
abstract: Idiopathic hypereosinophilic syndrome (HES) characterized by unexplained and persistent hypereosinophilia is heterogeneous and comprises several entities: a myeloproliferative form where myeloid lineages are involved with the interstitial chromosome 4q12 deletion leading to fusion between FIP1L1 and PDGFRA genes, the latter acquiring increased tyrosine kinase activity. And a lymphocytic variant, where hypereosinophilia is secondary to a primitive T lymphoid disorder demonstrated by the presence of a circulating T-cell clone. We performed molecular characterization of HES in 35 patients with normal karyotype by conventional cytogenetic analysis. TCRgamma gene rearrangements suggesting T clonality were seen in 11 (31%) patients, and FIP1L1-PDGFRA by RT-PCR in six (17%) of 35 patients, who showed no evidence of T-cell clonality. An elevated serum tryptase level was observed in FIP1L1-PDGFRA-positive patients responding to imatinib, whereas serum IL-5 levels were not elevated in T-cell associated hypereosinophilia. Sequencing FIP1L1-PDGFRA revealed scattered breakpoints in FIP1L1-exons (10-13), whereas breakpoints were restricted to exon 12 of PDGFRA. In the 29 patients without FIP1L1-PDGFRA, no activating mutation of PDGFRA/PDGFRB was detected; however; one patient responded to imatinib. FISH analysis of the 4q12 deletion was concordant with FIP1L1-PDGFRA RT-PCR data. Further investigation of the nature of FIP1L1-PDGFRA affected cells will improve the classification of HES.
authors.affiliation: Institut de Recherche contre le Cancer, Inserm U524, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Roche-Lestienne
authors.forename: S
authors.initials: S
authors.lastname: Lepers
authors.forename: V
authors.initials: V
authors.lastname: Soenen-Cornu
authors.forename: J-E
authors.initials: JE
authors.lastname: Kahn
authors.forename: J-L
authors.initials: JL
authors.lastname: Laï
authors.forename: E
authors.initials: E
authors.lastname: Hachulla
authors.forename: F
authors.initials: F
authors.lastname: Drupt
authors.forename: A-L
authors.initials: AL
authors.lastname: Demarty
authors.forename: A-S
authors.initials: AS
authors.lastname: Roumier
authors.forename: M
authors.initials: M
authors.lastname: Gardembas
authors.forename: M
authors.initials: M
authors.lastname: Dib
authors.forename: N
authors.initials: N
authors.lastname: Philippe
authors.forename: N
authors.initials: N
authors.lastname: Cambier
authors.forename: S
authors.initials: S
authors.lastname: Barete
authors.forename: C
authors.initials: C
authors.lastname: Libersa
authors.forename: O
authors.initials: O
authors.lastname: Bletry
authors.forename: P-Y
authors.initials: PY
authors.lastname: Hatron
authors.forename: B
authors.initials: B
authors.lastname: Quesnel
authors.forename: C
authors.initials: C
authors.lastname: Rose
authors.forename: K
authors.initials: K
authors.lastname: Maloum
authors.forename: O
authors.initials: O
authors.lastname: Blanchet
authors.forename: P
authors.initials: P
authors.lastname: Fenaux
authors.forename: L
authors.initials: L
authors.lastname: Prin
authors.forename: C
authors.initials: C
authors.lastname: Preudhomme
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001549:Benzamides; D002872:Chromosome Deletion; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D020732:Cytogenetic Analysis; D005091:Exons; D005260:Female; D005602:France; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D015848:Interleukin-5 / Q000097:blood; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D012697:Serine Endopeptidases / Q000097:blood; D053802:Tryptases
chemical_list: D001549:Benzamides; D015848:Interleukin-5; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D012697:Serine Endopeptidases; D053802:Tryptases