Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics.
Leukemia
; 19(5): 792-8, 2005 May.
Article
en En
| MEDLINE
| ID: mdl-15772698
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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Deleción Cromosómica
/
Síndrome Hipereosinofílico
/
Análisis Citogenético
Límite:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Leukemia
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2005
Tipo del documento:
Article
País de afiliación:
Francia