Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics
| Autor: | Mamoun Dib, Olivier Bletry, Christian Rose, Demarty Al, B. Quesnel, Catherine Roche-Lestienne, Odile Blanchet, Eric Hachulla, Pierre Fenaux, Jean-Luc Laï, Nathalie Philippe, Christian Libersa, Claude Preudhomme, Jean-Emmanuel Kahn, Martine Gardembas, Francois Drupt, Maloum K, Roumier As, Pierre-Yves Hatron, Soenen-Cornu, Lionel Prin, S. Lepers, Barete S, Nathalie Cambier |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Myeloid Adolescent Molecular Sequence Data Hypereosinophilia PDGFRB PDGFRA Biology Piperazines Hypereosinophilic Syndrome medicine Humans Kinase activity In Situ Hybridization Fluorescence Aged Aged 80 and over Chronic eosinophilic leukemia Chromosomes Human Pair 12 Base Sequence Serine Endopeptidases Imatinib Hematology Exons Sequence Analysis DNA Middle Aged medicine.disease digestive system diseases Imatinib mesylate medicine.anatomical_structure Pyrimidines Oncology Benzamides Cytogenetic Analysis Imatinib Mesylate Female Tryptases France medicine.symptom Chromosome Deletion Chromosomes Human Pair 4 Interleukin-5 medicine.drug |
| Zdroj: | Leukemia. 19(5) |
| ISSN: | 0887-6924 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|