Myeloid and Lymphoid Neoplasms with Eosinophilia and Abnormalities of PDGFRA and PDGFRB by FISH
FIP1L1/PDGFRA fusion for del(4q)(q12), PDGFRB gene rearrangement, FGFR1/CEP8, Please contact the Cytogenetics Laboratory if assistance with ordering in EPIC or SOFT is needed.
Specimen Collection Criteria
Collect: Peripheral blood or bone marrow aspirate in a Dark Green-top Sodium Heparin tube. (Min: 1.0 mL)
A copy of the requisition must be sent with the specimen.
Physician Office/Drawsite Specimen Preparation
Do not freeze specimen. Maintain specimens at room temperature (20-25°C or 68-77°F) prior to courier pickup. For delays in transport (greater than 48 from the time of collection), refrigerate (2-8°C or 36-46°F) the specimen.
Preparation for Courier Transport
Transport: Peripheral blood or bone marrow, at room temperature (20-26°C or 68-78.8°F) or refrigerated (2-8°C or 36-46°F).
- Specimens arriving in the Laboratory 4 days or more following the original collection date.
- Fixed or frozen specimens.
Specimen Stability for Testing:
Room Temperature (20-26°C or 68-78.8°F): 48 hours
Refrigerated (2-8°C or 36-46°F): 96 hours
Frozen (-20°C/-4°F or below): Unacceptable
Specimen Storage in Department Prior to Disposal:
Refrigerated (2-8°C or 36-46°F): 7 days. A backup cell pellet is maintained for three weeks after the case has been signed out for all peripheral blood specimens
Royal Oak Clinical Cytogenomics Laboratory.
Monday - Friday, 8:00 a.m. - 5:00 p.m.
Results available within 7 days of receipt in the Laboratory.
Positive or negative for a neoplastic clone. An interpretative report will be provided.
Fluorescence In Situ Hybridization (FISH) Analysis.
A positive FISH result indicates deletion of the CHIC2 gene which lies between the FIP1L1 and PDGFRa loci in band 4q12. Deletion of this gene is thus a surrogate marker for FIP1L1/PDGFRa fusion. Because of the genetic heterogeneity of these disorders, a negative result does not preclude the diagnosis of either HES or SMCD.
Myeloproliferative and lymphoid neoplasms associated with rearrangement of either PDGFRA or PDGFRB genes are generally characterized by eosinophilia. Both PDGFRA and PDGFRB rearrangements result in formation of an aberrant tyrosine kinase. In PDGFRA-related disorders, the clinical presentation is usually as chronic eosinophilic leukemia with prominent involvement of the mast cell lineage and sometimes of the neutrophil lineage. Less often, the presentation is as an AML or precursor T-lymphoblastic leukemia, both with eosinophilia. In PDGFRB-related disorders, the presentation can be that of a chronic myelomonocytic leukemia with eosinophilia. The importance of recognizing these disorders lies in the fact that, because rearrangements of both PDGFRA and PDGFRB result in an aberrant tyrosine kinase, their associated diseases can be responsive to tyrosine kinase inhibitors such as imatinib mesylate. By contrast, other diseases with either eosinophilia such as chronic eosinophilic leukemia NOS (hypereosinophilic syndrome) or mast cell involvement such as systemic mastocytosis do not demonstrate PDGFRA and PDGFRB rearrangement and so would not benefit from imatinib. Rearrangement of the FGFR1 gene on chromosome 8p11 is associated with the WHO Classification: “Myeloid and lymphoid neoplasms with FGFR1 abnormalities.”
PDGFRA rearrangement results in formation of a fusion tyrosine kinase FIP1L1/PDGFRA. This fusion gene is the consequence of a cryptic 800kb interstitial deletion within chromosome band 4q12 that deletes the CHIC2 (cysteine-rich hydrophobic domain 2) gene. Detection of deletion of the gene, which lies between FIP1L1 and PDGFRA loci is a surrogate marker for FIP1L1/PDGFRA fusion. Because the submicroscopic del(4q) is not observed in conventional cytogenetic analysis, a FISH assay to identify it is necessary. This assay utilizes a tri color LSI 4q12 rearrangement probe that detects deletion of the CHIC2 gene. FISH identification of a PDGFRB rearrangement utilizes a two-color DNA probe which spans the PDGFRB locus and splits into two separate colors when the gene is rearranged. FISH identification of an FGFR1 gene rearrangement utilizes a breakapart strategy which detects FGFR1 rearrangement along with a control probe for chromosome 8 enumeration.
- Pardanani A et al (2003): CHIC2 deletion: a surrogate for FIP1L1-PDGFRa fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Blood 102(9): 3093-3096.
- Cools J et al (2004): The FIP1L1-PDGFRa kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia. Cur Opin Hematol 11(1): 51-57.
88271x4 (DNA probe, each), 88275x3 (Interphase analysis, 100-300 cells).
Please contact the Cytogenetics Laboratory if assistance with ordering in EPIC or SOFT is needed.