Detection of the FIP1L1-PDGFRA fusion in idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia.

Idiopathic hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL) are related hematological malignancies characterized by sustained, unexplained hypereosinophilia (>1,500 eosinophils/microL). The term CEL is used when there is evidence that the disease is of clonal origin. We recently identified the FIP1L1-PDGFRA fusion gene in approx 50% of HES/CEL cases. Fusion of FIP1L1 to PDGFRA is the consequence of a deletion on chromosome 4, del(4)(q12q12), with the centromeric breakpoint in FIP1L1 and the telomeric breakpoint in PDGFRA. The breakpoints in FIP1L1 are diverse (introns 7 to 10), but the breakpoints in PDGFRA are always in exon 12 (encoding the juxtamembrane region). Because the chromosomal deletion is only 800 kb in size, it remains undetected with standard cytogenetics. In agreement with this, most patients with HES/CEL present with a normal karyotype. Here we describe three different techniques to detect the presence of the FIP1L1-PDGFRA fusion gene in peripheral blood or bone marrow cells.