Eosinophilia sometimes occurs in acute myeloid leukemia (AML), especially in core binding factor (CBF) leukemia. However, the pathogenesis of the differentiation from leukemic progenitors to eosinophils is not well understood in this type of leukemia. Recent reports showed that a novel fusion tyrosine kinase, Fip1-like1 (FIP1L1) platelet-derived growth factor receptor alpha (PDGFRalpha), is found in idiopathic hypereosinophilic syndrome. The involvement of another chimeric gene, PDGFRbeta, was also reported in myeloproliferative disorder with eosinophilia. These chimeric genes cause constitutive activation of PDGFR tyrosine kinases. On the other hand, a two-hit model for the pathogenesis of AML, which seems to be caused by inactivating mutations in transcription factors and genetic lesions in tyrosine kinase resulting in constitutive activation, has been proposed. On the basis of these findings, we screened for the expression of the FIP1L1-PDGFRalpha fusion gene and for mutations in the juxtamembrane and tyrosine kinase domains of PDGFRalpha/beta genes in 22 cases of CBF leukemia with eosinophilia. Among these cases, no FIP1L1-PDGFRalpha fusion gene was found. Although cDNA sequencing also detected three types of single-nucleotide alterations at kinase domains in PDGFRalpha/beta genes, all of them were silent changes and polymorphisms. Therefore, PDGFRalpha/beta genes do not appear to play a significant pathogenetic role in eosinophilia or leukemogenesis of CBF leukemia.