FIP1L1/PDGFR alpha-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.
Yamada
Yoshiyuki
Y
Division of Allergy and Immunology, Gunma Children's Medical Center, Shibukawa, Gunma, Japan. yamaday @ gcmc.pref.gunma.jp
Cancelas
Jose A
JA
D000818:Animals; D004802:Eosinophilia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D034721:Mastocytosis, Systemic / Q000150:complications / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics / Q000378:metabolism*
D015514:Oncogene Proteins, Fusion; D039221:mRNA Cleavage and Polyadenylation Factors; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha