Titre
Identification of a novel imatinib responsive KIF5B-PDGFRA fusion gene following screening for PDGFRA overexpression in patients with hypereosinophilia
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Score, J.
Auteure/Auteur
Curtis, C.
Auteure/Auteur
Waghorn, K.
Auteure/Auteur
Stalder, M.
Auteure/Auteur
Jotterand, M.
Auteure/Auteur
Grand, F. H.
Auteure/Auteur
Cross, N. C.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0887-6924
Statut éditorial
Publié
Date de publication
2006-05
Volume
20
Numéro
5
Première page
827
Dernière page/numéro d’article
32
Notes
Case Reports
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Résumé
Idiopathic hypereosinophilic syndrome (IHES) is a disease that is difficult to classify, and diagnosis is one of exclusion. The identification of a cytogenetically invisible interstitial deletion resulting in the fusion of FIP1-Like-1 (FIP1L1) to platelet-derived growth factor receptor alpha (PDGFRA) has enabled many IHES cases to be reclassified as chronic eosinophilic leukemia. As it is likely that PDGFRA may fuse to other partner genes, we established a reverse transcriptase-PCR test to detect specific overexpression of the PDGFRA kinase domain as an indicator of the presence of a fusion gene. Overexpression was detected in 12/12 FIP1L1-PDGFRA-positive patients, plus 9/217 (4%) patients with hypereosinophilia who had tested negative for FIP1L1-PDGFRA. One of the positive cases was investigated in detail and found to have a complex karyotype involving chromosomes 3, 4 and 10. Amplification of the genomic breakpoint by bubble PCR revealed a novel fusion between KIF5B at 10p11 and PDGFRA at 4q12. Imatinib, a known inhibitor of PDGFRalpha, produced a complete cytogenetic response and disappearance of the KIF5B-PDGFRA fusion by PCR, from both genomic DNA and mRNA. This study demonstrates the utility of screening for PDGFRA kinase domain overexpression in patients with IHES and has identified a third PDGFRA fusion partner in chronic myeloproliferative disorders.
Sujets
PID Serval
serval:BIB_0A89470D448A
PMID
Open Access
Oui
Date de création
2008-01-25T13:18:10.340Z
Date de création dans IRIS
2025-05-20T19:28:44Z