| Autor: |
Pardanani, Animesh, Ketterling, Rhett P., Brockman, Stephanie R., Flynn, Heather C., Paternoster, Sarah F., Shearer, Brandon M., Reeder, Terra L., Li, Chin-Yang, Cross, Nicholas C.P., Cools, Jan, Gilliland, D. Gary, Dewald, Gordon W., Tefferi, Ayalew |
| Zdroj: |
Blood; November 2003, Vol. 102 Issue: 9 p3093-3096, 4p |
| Abstrakt: |
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 CHIC2locus at 4q12 as a surrogate for the FIP1L1-PDGFRAfusion. CHIC2deletion 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-PDGFRArearrangement achieved a sustained complete response with imatinib mesylate therapy, the other two, both carrying the c-kitAsp816 to Val (Asp816Val) mutation, did not. These observations suggest that the FIP1L1-PDGFRArearrangement 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-PDGFRArearrangement and Asp816Val mutation will advance rational therapy decisions in SMCD. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
