HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Discovery of a fusion kinase in EOL-1 cells and idiopathic hypereosinophilic syndrome.

Abstract
Idiopathic hypereosinophilic syndrome (HES) is a myeloproliferative disease of unknown etiology. Recently, it has been reported that imatinib mesylate (Gleevec), an inhibitor of Bcr-Abl kinase useful in the treatment of chronic myeloid leukemia, is also effective in treating HES; however, the molecular target of imatinib in HES is unknown. This report identifies a genetic rearrangement in the eosinophilic cell line EOL-1 that results in the expression of a fusion protein comprising an N-terminal region encoded by a gene of unknown function with the GenBank accession number NM_030917 and a C-terminal region derived from the intracellular domain of the platelet-derived growth factor receptor alpha (PDGFRalpha). The fusion gene was also detected in blood cells from two patients with HES. We propose naming NM_030917 Rhe for Rearranged in hypereosinophilia. Rhe-PDGFRalpha fusions result from an apparent interstitial deletion that links Rhe to exon 12 of PDGFRalpha on chromosome 4q12. The fusion kinase Rhe-PDGFRalpha is constitutively phosphorylated and supports IL-3-independent growth when expressed in BaF3 cells. Proliferation and viability of EOL-1 and BaF3 cells expressing Rhe-PDGFRalpha are ablated by the PDGFRalpha inhibitors imatinib, vatalanib, and THRX-165724.
AuthorsJohn H Griffin, Joey Leung, Rebecca J Bruner, Michael A Caligiuri, Roger Briesewitz
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 100 Issue 13 Pg. 7830-5 (Jun 24 2003) ISSN: 0027-8424 [Print] United States
PMID12808148 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antineoplastic Agents
  • Benzamides
  • Enzyme Inhibitors
  • Indoles
  • Peptides
  • Phthalazines
  • Piperazines
  • Pyridines
  • Pyrimidines
  • Pyrroles
  • Recombinant Fusion Proteins
  • THRX 165724
  • Tyrosine
  • vatalanib
  • Imatinib Mesylate
  • Receptor, Platelet-Derived Growth Factor alpha
Topics
  • Adult
  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Base Sequence
  • Benzamides
  • Blotting, Western
  • Cell Division
  • Cell Line
  • Cell Survival
  • Cell Transformation, Neoplastic
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors (pharmacology)
  • Eosinophils (metabolism)
  • Gene Deletion
  • Humans
  • Hypereosinophilic Syndrome (blood, drug therapy, enzymology)
  • Imatinib Mesylate
  • Indoles (pharmacology)
  • Male
  • Mice
  • Models, Chemical
  • Models, Genetic
  • Molecular Sequence Data
  • Peptides (chemistry)
  • Phthalazines (pharmacology)
  • Piperazines (pharmacology)
  • Precipitin Tests
  • Protein Structure, Tertiary
  • Pyridines (pharmacology)
  • Pyrimidines (pharmacology)
  • Pyrroles (pharmacology)
  • Receptor, Platelet-Derived Growth Factor alpha (chemistry)
  • Recombinant Fusion Proteins (genetics, metabolism)
  • Recurrence
  • Tyrosine (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: