, Volume 86, Issue 12, pp 855-863
Date: 15 Aug 2007

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

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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.

Akiko Sada, Shin Okuyama, Hideshi Nakata, Hirotoshi Shimada, Kazuo Oshimi, Mayumi Mori, and Toshimitsu Matsui are members of the Japanese Elderly Leukemia and Lymphoma Study Group (JELLSG).