Lymphoid and Myeloid Neoplasm with Eosinophilia


This is a specific group of rare disorders that typically present as a myeloproliferative neoplasm with variable frequency of lymphoid neoplasm. The phenotype is caused by a rearrangement in either PDGFRA, PDGFRB, JAK2 or FGFR1 that results in an aberrant tyrosine kinase fusion gene. 

Patients with rearrangements of PDGFRA generally present with chronic eosinophilic leukemia (CEL), however acute presentation and presentation of eosinophilia with T-lymphoblastic lymphoma also occur. PDGFRA rearrangements identified by FISH analysis are present in 10-20% of all CEL cases. The most common rearrangement results in a cytogenetically cryptic deletion within 4q12 which results in the fusion of the 5’ portion of the FIP1L1 gene (variable break-points) with the 3’PDGFRA gene. Patients with a PDGFRA mutation respond to imatinib.

Patients with rearrangements of PDGFRB generally have a chronic myelomonocytic leukemia presentation, usually with eosinophilia, although patients may have peripheral blood eosinophils <1.5 x109.  The most common PDGFRB rearrangement is t(5;12)(q21-33;p12) which generates an ETV6-PDGFRB fusion gene, although many other PDGFRB rearrangements have been noted.  Patients with PDGFRB rearrangements respond to imatinib.

Patients with rearrangements of JAK2 often present with a lower eosinophila count compared to other genes rearrangements. The most common rearrangement t(8;9)(p22;p24.1) involving JAK2 and PCM1 is cytogenetically cryptic.  Other less common fusion partners include ETV6 or BCR.  Patients with a JAK2 rearrangement are not responsive to imatinib.

Patients with rearrangements of FGFR1 often present with an eosinophilia MPN in the bone marrow and many have lymphoma.  In patients that present with CEL, transformation to AML is common (including myeloid sarcoma), T or B linear lymphoblastic leukemia/lymphoma or mixed.  Up to 90% of patients will have eosinophilia of the peripheral blood and/or bone marrow.  A number of FGFR1 rearrangements have been reported with the most common being t(8;13)(p11;q12) involving ZNF198-FGFR1.  Patients with an FGFR1 rearrangement are not responsive to imatinib. 


  • Completed CGL Lymphoid Testing or CGL Myeloid Testing requisition form
  • One of the following specimens (please see our Specimen Guidelines, Cytogenetics FISH test type):
    • 4mL peripheral blood collected in sodium heparin tubes (green top)
    • 2×1.0 mL of marrow aspirate in 9mL media (RPMI 1640, 3.8% FBS, antibiotics)
  • Also accepted, but not preferred specimens include:
    • Bone marrow biopsy in 9mL media (RPMI 1640, 3.8% FBS, antibiotics)

  • The submitted specimen must meet AT LEAST ONE of the following requirements:
    • Peripheral eosinophil count over 1.5×109 at the time of diagnosis, and blasts representing fewer than 20% of cells in blood or bone marrow or;
    • Chronic myelomonocytic leukemia with a peripheral eosinophil count over 1.5×109 for six months or greater, and blasts representing fewer than 20% of cells in blood or bone marrow or;
    • Acute myeloid leukemia or precursor T-cell or C-cell lymphoblastic leukemia/lymphoma with PB or BM eosinophilia. 


Results are reported within fourteen days from receipt of specimen and completed requisition form.  


  • Results are reported as Positive or Negative for a rearrangement.
  • The absence of a rearrangement in one of these loci does not exclude a malignant myeloid/lymphoid abnormality.  


The submitted specimen is harvested into a methanol-acetic acid (MAA) fixed cell pellet. The pellet is used to perform FISH analysis on interphase nuclei, as well as metaphases if available. Four commercial probes are used to interrogate the loci of interest: a tri-colour rearrangement probe (Vysis) to PDGFRA, a dual colour, break-apart probe (Vysis) to PDGFRB, a dual colour break-apart probe (Empire Genomics) to JAK2, and a dual colour, break-apart probe (Empire Genomics) to FGFR1.


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