Abstract
Idiopathic hypereosinophilic syndrome (HES) characterized by unexplained and persistent hypereosinophilia is heterogeneous and comprises several entities: a myeloproliferative form where myeloid lineages are involved with the interstitial chromosome 4q12 deletion leading to fusion between FIP1L1 and PDGFRA genes, the latter acquiring increased tyrosine kinase activity. And a lymphocytic variant, where hypereosinophilia is secondary to a primitive T lymphoid disorder demonstrated by the presence of a circulating T-cell clone. We performed molecular characterization of HES in 35 patients with normal karyotype by conventional cytogenetic analysis. TCRγ gene rearrangements suggesting T clonality were seen in 11 (31%) patients, and FIP1L1–PDGFRA by RT-PCR in six (17%) of 35 patients, who showed no evidence of T-cell clonality. An elevated serum tryptase level was observed in FIP1L1–PDGFRA-positive patients responding to imatinib, whereas serum IL-5 levels were not elevated in T-cell associated hypereosinophilia. Sequencing FIP1L1–PDGFRA revealed scattered breakpoints in FIP1L1-exons (10–13), whereas breakpoints were restricted to exon 12 of PDGFRA. In the 29 patients without FIP1L1–PDGFRA, no activating mutation of PDGFRA/PDGFRB was detected; however; one patient responded to imatinib. FISH analysis of the 4q12 deletion was concordant with FIP1L1–PDGFRA RT-PCR data. Further investigation of the nature of FIP1L1–PDGFRA affected cells will improve the classification of HES.
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Acknowledgements
We are grateful to V Dutoit for technical assistance, Dr A Reiters for new Fip1L1 numbering sequence, Dr Christophe Roumier for the design of BACs probes, and Dr M Rocchi and the Sanger Institute for providing genomic clones. We also are indebted to clinicians from the French eosinophil NetWork (Dr Vatan, Pr Le Bras, Pr Vincendeau, Pr Fialon, Dr Doermann from the CHU of Bordeaux; Pr Philippe, Dr Tournilhac, Dr Tridon from the CHU of Clermont-Ferrant; Pr Delaporte from the CHU of Lille; Dr Cozon, Pr Broussole from the CHU of Lyon, Pr Moneret-Vautrin, Dr Morisset, Dr Kohler from the CHU of Nancy; Pr Merle-Beral, Dr Choquet from the Hopital de la Pitié-Salpêtrière; Pr Arlet, Pr Abbal from the CHU of Toulouse). This work was supported by the Cancéropôle de Lille.
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Roche-Lestienne, C., Lepers, S., Soenen-Cornu, V. et al. Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics. Leukemia 19, 792–798 (2005). https://doi.org/10.1038/sj.leu.2403722
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DOI: https://doi.org/10.1038/sj.leu.2403722
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