Identification of a novel imatinib responsive KIF5B-PDGFRA fusion gene following screening for PDGFRA overexpression in patients with hypereosinophilia
Details
Serval ID
serval:BIB_0A89470D448A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of a novel imatinib responsive KIF5B-PDGFRA fusion gene following screening for PDGFRA overexpression in patients with hypereosinophilia
Journal
Leukemia
ISSN
0887-6924 (Print)
Publication state
Published
Issued date
05/2006
Volume
20
Number
5
Pages
827-32
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
Abstract
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.
Keywords
Antineoplastic Agents/*pharmacology/therapeutic use
Cohort Studies
*Gene Expression Regulation, Neoplastic/drug effects
Gene Rearrangement
*Genetic Screening
Humans
Hypereosinophilic Syndrome/drug therapy/*genetics
In Situ Hybridization, Fluorescence
Male
Middle Aged
Oncogene Fusion/*genetics
Piperazines/*pharmacology/therapeutic use
Protein-Tyrosine Kinases/drug effects/*genetics
Pyrimidines/*pharmacology/therapeutic use
RNA, Messenger/drug effects/genetics
Receptor, Platelet-Derived Growth Factor alpha/antagonists &
inhibitors/*genetics
Remission Induction
Reverse Transcriptase Polymerase Chain Reaction/methods
Sensitivity and Specificity
Treatment Outcome
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 15:18
Last modification date
20/08/2019 13:32