Annals of Hematology

, Volume 86, Issue 12, pp 855–863 | Cite as

A multicenter analysis of the FIP1L1-αPDGFR fusion gene in Japanese idiopathic hypereosinophilic syndrome: an aberrant splicing skipping the αPDGFR exon 12

  • Akiko Sada
  • Yoshio Katayama
  • Katsuya Yamamoto
  • Shin Okuyama
  • Hideshi Nakata
  • Hirotoshi Shimada
  • Kazuo Oshimi
  • Mayumi Mori
  • Toshimitsu Matsui
  • Japanese Elderly Leukemia and Lymphoma Study Group (JELLSG)
Original Article


To study the clinical characteristics of hypereosionophilic syndrome and chronic eosinophilic leukemia (HES/CEL) in Japan, the clinical data of 29 HES/CEL patients throughout the country were surveyed. Moreover, the involvement of the FIP1L1-αPDGFR fusion gene resulting from a cryptic del (4)(q12q12) was examined in 24 cases. The FIP1L1-αPDGFR messenger RNA (mRNA) was detected in three patients (13% of patients fulfilled WHO criteria and 17% of Chusid criteria). One had a novel fusion transcript, which skipped the exon 12 of αPDGFR. The transcript appears to be generated by a splicing mechanism that is different from the previously reported splicing patterns. In silico analysis, the exon skipping was not related to a disruption of the exonic splicing enhancers within the exon but strongly associated with the loss of the vast majority of the FIP1L intron 8a where intronic splicing enhancers were accumulated. Unexpectedly, pseudo-chimera DNA fragments with some shared characteristic features were occasionally generated from healthy control samples by reverse transcriptase polymerase chain reaction (RT-PCR). Considering the relatively low incidence of the FIP1L1-αPDGFR transcript positive case, extreme care must therefore be taken when making a diagnosis using RT-PCR before imatinib therapy.


Hypereosionophilic syndrome Imatinib FIP1L1-αPDGFR RT-PCR Exon skipping Alternative splicing CEL 



We gratefully acknowledge the assistance of collaborating physicians and investigators for their participation in the clinical and biologic characterization of patients.


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Akiko Sada
    • 1
  • Yoshio Katayama
    • 1
  • Katsuya Yamamoto
    • 1
  • Shin Okuyama
    • 2
  • Hideshi Nakata
    • 3
  • Hirotoshi Shimada
    • 4
  • Kazuo Oshimi
    • 5
  • Mayumi Mori
    • 6
  • Toshimitsu Matsui
    • 1
  • Japanese Elderly Leukemia and Lymphoma Study Group (JELLSG)
  1. 1.Hematology/Oncology, Department of MedicineKobe University Graduate School of MedicineKobeJapan
  2. 2.Department of MedicineAkita University School of MedicineAkitaJapan
  3. 3.Department of MedicineKochi Medical SchoolKochiJapan
  4. 4.Department of MedicineKyushu University School of MedicineFukuokaJapan
  5. 5.Hematology, Department of MedicineJuntendo University School of MedicineTokyoJapan
  6. 6.Tama Hokubu Medical CenterTokyoJapan

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