The clinical laboratory work-up confirmed secondary HE in 25 (20%) patients; myeloid/lymphoid neoplasms with rearrangements of PDGFRA (n = 9) or PDGFRB (n = 2) (9%); HE associated with a well-defined myeloid neoplasm in 8 (6%); and abnormal bone marrow and/or molecular genetic abnormalities consistent with chronic eosinophilic leukemia (CEL), not otherwise specified (NOS) in 21 (17%) patients.
Testing for a FIP1L1-PDGFRA rearrangement is at present limited to patients with idiopathic hypereosinophilia, and we hypothesize that this abnormality may be under-diagnosed in children with acute leukemias.
Chronic eosinophilic leukaemia associated with the FIP1L1-PDGFRA fusion gene (F/P+ CEL) is a rare cause of marked persistent hypereosinophilia, arising almost exclusively in male patients.
Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) have been described in various tumors, including FIP1L1-PDGFRα in patients with myeloproliferative diseases associated with hypereosinophilia and the PDGFRα(D842V) mutant in gastrointestinal stromal tumors and inflammatory fibroid polyps.
The Fip1-like1 (FIP1L1)-platelet-derived growth factor receptor alpha fusion gene (F/P) arising in the pluripotent hematopoietic stem cell (HSC),causes 14% to 60% of patients with hypereosinophilia syndrome (HES).
ETV6-PDGFRB (also called TEL-PDGFRB) and FIP1L1-PDGFRA are receptor-tyrosine kinase fusion genes that cause chronic myeloid malignancies associated with hypereosinophilia.
FIP1L1/PDGFR alpha-positive disorders are characterized by clonal hypereosinophilia, multiple organ dysfunctions due to eosinophil infiltration, systemic mastocytosis (SM) and a dramatic response to treatment with imatinib mesylate.
Despite patients with FIP1-like-1-platelet-derived growth factor alpha (FIP1L1-PDGFRA) associated HES (myeloid neoplasms associated with PDGFRA rearrangement) have been shown to respond to low-dose imatinib with a complete and durable hematological and cytogenetic remission, influences of imatinib on clinical manifestations related to hypereosinophilia heart involvement are variable.
Furthermore, the same FIP1L1-PDGFRA rearrangement was identified in patients with hypereosinophilia and atypical mast cell proliferations, raising the question of a disease with two concomitant lines of differentiation.
The year 2008 marks the fifth anniversary since the publication which identified the FIP1L1-PDGFRA fusion gene in patients with idiopathic hypereosinophilia.
Overexpression was detected in 12/12 FIP1L1-PDGFRA-positive patients, plus 9/217 (4%) patients with hypereosinophilia who had tested negative for FIP1L1-PDGFRA.
An elevated serum tryptase level was observed in FIP1L1-PDGFRA-positive patients responding to imatinib, whereas serum IL-5 levels were not elevated in T-cell associated hypereosinophilia.
The discovery of the FIP1L1-PDGFRA fusion gene has led to the recognition that many patients who would previously have been regarded as having idiopathic hypereosinophilia actually have chronic eosinophilic leukemia.
Detection of the FIP1L1-PDGFRA fusion gene or the corresponding cryptic 4q12 deletion supports the diagnosis of chronic eosinophilic leukemia (CEL) in patients with chronic hypereosinophilia.