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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3093-3096. Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2003-05-1627. This Article Full Text 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 Citation Map 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. Related Collections Oncogenes and Tumor Suppressors Clinical Trials and Observations Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate 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 From the Divisions of Hematology and Internal Medicine, Laboratory Genetics, and Hematopathology, Mayo Clinic, Rochester, MN; Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, United Kingdom; and Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Imatinib mesylate is effective in the treatment of hematologic 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 (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 (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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