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rdf:type |
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lifeskim:mentions |
umls-concept:C0014457,
umls-concept:C0087111,
umls-concept:C0221013,
umls-concept:C0332281,
umls-concept:C0332466,
umls-concept:C0681842,
umls-concept:C0871261,
umls-concept:C0939537,
umls-concept:C1413390,
umls-concept:C1442161,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C1709305,
umls-concept:C2911692
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pubmed:issue |
9
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pubmed:dateCreated |
2003-10-21
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pubmed:abstractText |
Imatinib mesylate is effective in the treatment of hematologic malignancies that are characterized by either abl- or PDGFR beta- activating mutations. The drug is also active in a subset of patients with eosinophilic disorders and systemic mast cell disease (SMCD). Recently, a novel tyrosine kinase that is generated from fusion of the Fip1-like 1 (FIP1L1) and PDGFR alpha (PDGFRA) genes has been identified as a therapeutic target for imatinib mesylate in hypereosinophilic syndrome (HES). We used fluorescence in situ hybridization (FISH) to detect deletion of the CHIC2 locus at 4q12 as a surrogate for the FIP1L1-PDGFRA fusion. CHIC2 deletion was observed in bone marrow cells for 3 of 5 patients with SMCD associated with eosinophilia. Deletion of this locus and expression of the FIP1L1-platelet-derived growth factor receptor alpha (PDGFRA) fusion was also documented in enriched eosinophils, neutrophils, or mononuclear cells by both FISH and reverse transcriptase-polymerase chain reaction (RT-PCR) for one patient. While all 3 patients with the FIP1L1-PDGFRA rearrangement achieved a sustained complete response with imatinib mesylate therapy, the other two, both carrying the c-kit Asp816 to Val (Asp816Val) mutation, did not. These observations suggest that the FIP1L1-PDGFRA rearrangement occurs in an early hematopoietic progenitor and suggests that the molecular pathogenesis for a subset of SMCD patients is similar to that of HES. Screening for the FIP1L1-PDGFRA rearrangement and Asp816Val mutation will advance rational therapy decisions in SMCD.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/FIP1L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/FIP1L1-PDGFRA fusion protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Fusion,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Platelet-Derived Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/imatinib,
http://linkedlifedata.com/resource/pubmed/chemical/mRNA Cleavage and Polyadenylation...
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-4971
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pubmed:author |
pubmed-author:BrockmanStephanie RSR,
pubmed-author:CoolsJanJ,
pubmed-author:CrossNicholas C PNC,
pubmed-author:DewaldGordon WGW,
pubmed-author:FlynnHeather CHC,
pubmed-author:GillilandD GaryDG,
pubmed-author:KetterlingRhett PRP,
pubmed-author:LiChin-YangCY,
pubmed-author:PardananiAnimeshA,
pubmed-author:PaternosterSarah FSF,
pubmed-author:ReederTerra LTL,
pubmed-author:ShearerBrandon MBM,
pubmed-author:TefferiAyalewA
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
102
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3093-6
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12842979-Adult,
pubmed-meshheading:12842979-Aged,
pubmed-meshheading:12842979-Aged, 80 and over,
pubmed-meshheading:12842979-Eosinophilia,
pubmed-meshheading:12842979-Gene Rearrangement,
pubmed-meshheading:12842979-Hematopoietic Stem Cells,
pubmed-meshheading:12842979-Humans,
pubmed-meshheading:12842979-Hypereosinophilic Syndrome,
pubmed-meshheading:12842979-In Situ Hybridization, Fluorescence,
pubmed-meshheading:12842979-Mastocytosis, Systemic,
pubmed-meshheading:12842979-Middle Aged,
pubmed-meshheading:12842979-Oncogene Proteins, Fusion,
pubmed-meshheading:12842979-Piperazines,
pubmed-meshheading:12842979-Predictive Value of Tests,
pubmed-meshheading:12842979-Prospective Studies,
pubmed-meshheading:12842979-Pyrimidines,
pubmed-meshheading:12842979-Receptor, Platelet-Derived Growth Factor alpha,
pubmed-meshheading:12842979-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12842979-Sequence Deletion,
pubmed-meshheading:12842979-Treatment Outcome,
pubmed-meshheading:12842979-mRNA Cleavage and Polyadenylation Factors
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pubmed:year |
2003
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pubmed:articleTitle |
CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy.
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pubmed:affiliation |
Division of Hematology and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
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pubmed:publicationType |
Journal Article
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