title: Chronic eosinophilic leukemia with the FIP1L1-PDGFRalpha fusion gene in a patient with a history of combination chemotherapy.
abstract: Hypereosinophilic syndrome (HES) was diagnosed in December 2000 in a 43-year-old man on the basis of persistent eosinophilia (11.7 x 10(9)/L) and a normal karyotype of the bone marrow cells. He had developed intra-abdominal non-Hodgkin's lymphoma and in 1992 had received 3 courses of combination chemotherapy with doxorubicin (Adriamycin), cyclophosphamide, vincristine, methotrexate, bleomycin, and prednisolone. The patient was orally given prednisolone (10 mg/day) and cyclophosphamide (50 mg/day) as HES treatment without a subsequent improvement of the eosinophilia. In May 2003, anemia (hemoglobin, 7.9 g/dL) and thrombocytopenia (65 x 10(9)/L) manifested with progressive eosinophilia (21.0 x 10(9)/L) and a small number of blasts. The patient became febrile and was admitted in July 2003. Cytogenetic reexamination of the bone marrow cells disclosed the deletion of 4q12, indicating the presence of a fusion of the Fip1-like 1 (FIP1L1) gene to the plateletderived growth factor receptor alpha (PDGFRalpha) gene and consequently the clonal nature of his hematopoietic cells. DNA sequence analysis demonstrated that the breakpoints of the FIP1L1 and PDGFRalpha genes were present in exon 9 and exon 12, respectively. Treatment with imatinib mesylate (300 mg/day) promptly brought about complete remission. Although a number of similar eosinophilic cases have been reported, our patient may be the first such patient with a history of chemotherapy.
authors.affiliation: Department of Hematology and Clinical Immunology, Kobe City General Hospital, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurata
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Togami
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Fujita
authors.forename: Naoko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsushita
authors.forename: Akinori
authors.initials: A
authors.lastname: Maeda
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nagai
authors.forename: Akiko
authors.initials: A
authors.lastname: Sada
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Matsui
authors.forename: Takayuki
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001549:Benzamides; D002908:Chronic Disease; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000139:chemically induced / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics; D000068877:Imatinib Mesylate; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000188:drug therapy; D008297:Male; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D017422:Sequence Analysis, DNA; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics*
chemical_list: D001549:Benzamides; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011743:Pyrimidines; D039221:mRNA Cleavage and Polyadenylation Factors; D000068877:Imatinib Mesylate; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha