FIP1L1/PDGFRα-Associated Systemic Mastocytosis

Since the identification of the FIP1L1/PDGFRA fusion gene as a pathogenic cause of the hypereosinophilic syndrome (HES), the importance of the molecular classification of HES leading to the diagnosis of chronic eosinophilic leukemia (CEL) has been recognized. As a result, a new category, 'myeloid and lymphoid neoplasm with eosinophilia and abnormalities in PDGFRA, PDGFRB or FGFR1', has recently been added to the new WHO criteria for myeloid neoplasms. 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. A murine HES/CEL model by the introduction of FIP1L1/PDGFR alpha and IL-5 overexpression also shows SM, representing patients with FIP1L1/PDGFR alpha-positive HES/CEL/SM. The murine model and the in vitro development system of FIP1L1/PDGFR alpha-positive mast cells revealed the interaction between FIP1L1/PDGFR alpha, IL-5 and stem cell factor in the development of HES/CEL/SM. Current findings of FIP1L1/PDGFR alpha-positive HES/CEL are reviewed focusing on aberrant mast cell development leading to SM.