However, after treatment with hydroxyurea and serial phlebotomies had been started, the patient developed hypereosinophilia, fitting the category of a myeloproliferative neoplasm with eosinophilia associated with the FIP1L1-PDGFRA gene fusion, as confirmed by molecular analysis.
We studied a new FISH method to detect CHIC2 deletion, FIP1L1/PDGFRA fusion and PDGFRA translocation in patients with myeloid neoplasms associated with eosinophilia.
Similarly, the drug has now been shown to display equally impressive therapeutic activity in eosinophilia-associated chronic myeloproliferative disorders that are characterized by activating mutations of either the PDGFRB or the PDGFRA gene.
The myeloid and lymphoid neoplasms with eosinophilia and PDGFRA gene rearrangements usually show a good response to Imatinib and are typically associated with a normal karyotype, occasionally exhibiting a secondary chromosomal abnormality associated with clonal evolution.
FIP1L1-PDGFRA in eosinophilic disorders: prevalence in routine clinical practice, long-term experience with imatinib therapy, and a critical review of the literature.
In 2003, a karyotypically-occult FIP1L1-PDGFRA was reported in a subset of patients with blood eosinophilia and bone marrow mastocytosis; this mutation has since joined several other molecular markers for eosinophilic (e.g.
Examination for the common eosinophilia-related cytogenetic abnormalities involving the genes PDGFRA, PDGFRB, and FGFR1 together with BCR-ABL fusion gene was negative.
HES and CEL-NOC are considered distinct from molecularly defined eosinophilic disorders, such as those associated with activating mutations of PDGFR (PDGFRA and PDGFRB) and fibroblast growth factor receptor-1.
At diagnosis, all patients with known fusion genes involving PDGFRA (n=5; 51 patients) or PDGFRB (n=5; 7 patients) showed significantly increased normalized expression levels compared to 191 patients with fusion gene-negative eosinophilia or healthy individuals (PDGFRA/ABL: 0.73 versus 0.0066 versus 0.0064, P<0.0001; PDGFRB/ABL: 196 versus 3.8 versus 5.85, P<0.0001).
We genotyped six single-nucleotide polymorphisms (SNP) within or close to the IL5RA or IL5 genes in 82 patients with FIP1L1-PDGFRA-positive CEL plus, as controls, healthy individuals (n=100), patients with FIP1L1-PDGFRA-negative eosinophilia (n=100) or patients with chronic myeloid leukaemia (CML) (n=100).
Molecular studies were negative for Fip1-like1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA) translocation and PDGFRB and FGFR mutations, indicating nonclonal eosinophilia.
Complete remissions, in response to treatment with low-dose imatinib mesylate (100 mg/day or less) have now been documented in all cases of FIP1L1-PDGFRA(+) eosinophilic disorder as well as other eosinophilic disorders that carry activation mutations of the PDGFRB gene that is located on chromosome 5q33.
We present the first case of T acute lymphoblastic leukemia with a t(4;22)(q12;q11.2) involving the BCR and PDGFRA genes, without associated eosinophilia.
To assess the presence of genetic imbalances in patients with myeloproliferative neoplasms (MPNs), 38 patients with chronic eosinophilia were studied by array comparative genomic hybridization (aCGH): seven had chronic myelogenous leukaemia (CML), BCR-ABL1 positive, nine patients had myeloproliferative neoplasia Ph- (MPN-Ph-), three had a myeloid neoplasm associated with a PDGFRA rearrangement, and the remaining two cases were Lymphoproliferative T neoplasms associated with eosinophilia.
Imatinib is effective in patients with increased mast cells and eosinophils associated with FIP1L1/PDGFRA+ (e.g., myeloid neoplasm with eosinophilia and rearrangement of PDGFRA) or rare patients with SM associated with KIT mutations outside of exon 17.
Myeloid neoplasms with eosinophilia and abnormalities of the PDGFRA gene can benefit from therapy with tyrosine kinase inhibitors, therefore revealing the PDGFRA rearrangement is essential to ensure the best choice of treatment.
The presence of eosinophilia, although prevalent (34%), was prognostically neutral, and the overall results were not affected by exclusion of FIP1L1-PDGFRA-positive cases.
The purpose of this review is to provide an overview of the differential diagnosis for eosinophilia, to recommend specific steps for the pathologist evaluating blood and bone marrow, and to emphasize 2 important causes of eosinophilia that require specific ancillary tests for diagnosis: myeloproliferative neoplasm with PDGFRA rearrangement and lymphocyte-variant hypereosinophilic syndrome.
The transcript of FIP1L1-PDGFRA fusion gene is a genetic biomarker of clonal eosinophilia screened routinely by reverse transcript PCR (RT-PCR) during diagnosis.
The presence of a dominant neoplastic clone with FIP1L1-PDGFRA rearrangement was suspected on the basis of sudden onset of peripheral and bone marrow eosinophilia and confirmed by fluorescence in situ hybridization and molecular diagnostic tests.
Findings from our institutional experience support initial testing in isolated eosinophilia with otherwise unremarkable BM to include PDGFRA rearrangement, tryptase/CD25 immunohistochemistry, cytogenetics, and T-cell flow cytometry/receptor gene rearrangement.
Interestingly, elevated expression of Hes1 was found in two of five samples of Fip1-like1 platelet-derived growth factor receptor-α (FIP1L1-PDGFA)-positive myeloid neoplasms associated with eosinophilia.