CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy

DOI PDF 被引用文献12件
  • Animesh Pardanani
    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.
  • Rhett P. Ketterling
    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.
  • Stephanie R. Brockman
    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.
  • Heather C. Flynn
    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.
  • Sarah F. Paternoster
    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.
  • Brandon M. Shearer
    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.
  • Terra L. Reeder
    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.
  • Chin-Yang Li
    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.
  • Nicholas C. P. Cross
    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.
  • Jan Cools
    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.
  • D. Gary Gilliland
    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.
  • Gordon W. Dewald
    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.
  • 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.

抄録

<jats:title>Abstract</jats:title><jats:p>Imatinib mesylate is effective in the treatment of hematologic malignancies that are characterized by either abl- or PDGFRβ- 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 PDGFRα (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 α (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.</jats:p>

収録刊行物

  • Blood

    Blood 102 (9), 3093-3096, 2003-11-01

    American Society of Hematology

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