Current Concepts on the Pathogenesis of the Hypereosinophilic Syndrome/Chronic Eosinophilic Leukemia

Chronic eosinophilic leukemia is a clonal disease characterized by hypereosinophilia and eosinophilia-related pathologic manifestations. Recently, the fusion gene FIP1L1/PDGFRA was found in the long arm of chromosome 4 and its expression has been shown to be associated with development of a clinical hypereosinophilic syndrome (HES) in a significant proportion of patients. FIP1L1/PDGFRα, the product of the gene FIP1L1/PDGFRA, is a constitutively activated tyrosine kinase and can be inhibited by imatinib mesylate. Several investigations have tried to dissect the mechanism of leukemogenesis and signaling induced by FIP1L1/PDGFRα in cell lines, primary human eosinophils and in murine myeloproliferative models. In this review, we analyzed the current knowledge on the relationship between FIP1L1/PDGFRα-induced signaling and eosinophil proliferation, survival and activation, specially focusing on its possible role in the modulation of cytokine and chemoattractant signaling pathways.