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Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2003-05-1627. This Article Full Text (PDF) All Versions of this Article: 2003-05-1627v1 102/9/3093    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pardanani, A. Articles by Tefferi, A. Search for Related Content PubMed PubMed Citation Articles by Pardanani, A. Articles by Tefferi, A. Social Bookmarking                   What's this? Submitted May 21, 2003 Accepted June 22, 2003 CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to Imatinib therapy Animesh Pardanani, Rhett P Ketterling, Stephanie R Brockman, Heather C Flynn, Sarah F Paternoster, Brandon M Shearer, Terra L Reeder, Chin-Yang Li, Nicholas C P Cross, Jan Cools, D Gary Gilliland, Gordon W Dewald, and Ayalew Tefferi* Divisions of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA Division of Laboratory Genetics, Mayo Clinic, Rochester, MN, USA Division of Hematopathology, Mayo Clinic, Rochester, MN, USA Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wilts, United Kingdom Division of Hematology and Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United Kingdom * Corresponding author; email: tefferi.ayalew{at}mayo.edu. Imatinib mesylate (GleevecTM) is effective in the treatment of hematological malignancies that are characterized by either abl or PDGFR 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 genes has been identified as a therapeutic target for imatinib 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-PDGFR 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- PDGFR fusion was also documented in enriched eosinophils, neutrophils, or mononuclear cells by both FISH and RT-PCR for one patient. While all 3 patients with the FIP1L1- PDGFR rearrangement achieved a sustained complete response with imatinib therapy, the other two, both carrying the c-kit Asp816 to Val (D816V) mutation, did not. These observations suggest that the FIP1L1-PDGFR 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- PDGFR rearrangement and D816V mutation will advance rational therapy decisions in SMCD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H.-P. Horny Mastocytosis: An Unusual Clonal Disorder of Bone Marrow-Derived Hematopoietic Progenitor Cells Am J Clin Pathol, September 1, 2009; 132(3): 438 - 447. [Abstract] [Full Text] [PDF] K.-H. Lim, A. Tefferi, T. L. Lasho, C. Finke, M. Patnaik, J. H. Butterfield, R. F. McClure, C.-Y. Li, and A. 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