The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)–like disease

The severity of FIP1L1–PDGFRA-positive chronic eosinophilic leukaemia is associated with polymorphic variation at the IL5RA locus

“…7 If elevated IL-5 signalling is also important for human FIP1L1-PDGFRA-positive CEL, it is possible that constitutional differences in the expression or function of the IL-5 system may be associated with the development or severity of disease. Alternatively, abnormalities of this system may be acquired before or after the acquisition of the fusion gene.…”

“…6 However, when expressed in mice that had been engineered to overexpress IL-5, the absolute and relative eosinophil counts increased and tissue infiltration was observed. 7 These observations indicated that FIP1L1-PDGFRA alone is insufficient to induce true HES/CEL in mice, and that a secondary event associated with IL-5 overexpression is required for the full phenotype. Whether constitutional or acquired changes in IL-5 signalling are relevant to the human disease is unknown.…”

Five years since the discovery of FIP1L1–PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias

“…65 Expression of FIP1L1-PDGFRA together with overexpression of IL-5, however, mimics the disease much better in the mouse, with typical features of HES such as tissue infiltration of eosinophils. 67 Similarly, a study of polymorphic variation at the IL-5 receptor-a (IL5RA) gene revealed an association between a SNP in the 5 0 UTR of IL5RA and the eosinophil count/presence of tissue infiltration in FIP1L1-PDGFRA-positive HES patients. 68 These data suggest that FIP1L1-PDGFRA alone is not sufficient to explain the development of HES/CEL, and that additional factors such as IL-5 signaling may also be implicated or at least may influence the severity of the disease.…”

Gastrointestinal Eosinophilia

“…The FIP-L1-PDGFRA fusion gene cooperates with IL-5 overexpression in a murine model of HES, suggesting that both pathogenic events cooperate in disease etiology. [71] The patients generally responsive to imatinib are those most characteristic of "classic" HES, namely males between the ages of 20-50 who present clinically with marked peripheral blood eosinophilia. Recently, these patients have been shown to meet minor criteria for systemic mastocytosis, having elevated levels of serum mast cell tryptase, and high numbers of dysplastic mast cells in the bone marrow.…”