title: Molecular analysis of PDGFRalpha/beta genes in core binding factor leukemia with eosinophilia.
abstract: Eosinophilia sometimes occurs in acute myeloid leukemia (AML), especially in core binding factor (CBF) leukemia. However, the pathogenesis of the differentiation from leukemic progenitors to eosinophils is not well understood in this type of leukemia. Recent reports showed that a novel fusion tyrosine kinase, Fip1-like1 (FIP1L1) platelet-derived growth factor receptor alpha (PDGFRalpha), is found in idiopathic hypereosinophilic syndrome. The involvement of another chimeric gene, PDGFRbeta, was also reported in myeloproliferative disorder with eosinophilia. These chimeric genes cause constitutive activation of PDGFR tyrosine kinases. On the other hand, a two-hit model for the pathogenesis of AML, which seems to be caused by inactivating mutations in transcription factors and genetic lesions in tyrosine kinase resulting in constitutive activation, has been proposed. On the basis of these findings, we screened for the expression of the FIP1L1-PDGFRalpha fusion gene and for mutations in the juxtamembrane and tyrosine kinase domains of PDGFRalpha/beta genes in 22 cases of CBF leukemia with eosinophilia. Among these cases, no FIP1L1-PDGFRalpha fusion gene was found. Although cDNA sequencing also detected three types of single-nucleotide alterations at kinase domains in PDGFRalpha/beta genes, all of them were silent changes and polymorphisms. Therefore, PDGFRalpha/beta genes do not appear to play a significant pathogenetic role in eosinophilia or leukemogenesis of CBF leukemia.
authors.affiliation: Division of Hematology and Oncology, Mie University School of Medicine, Tsu, Mie, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Monma
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishii
authors.forename: Felipe
authors.initials: F
authors.lastname: Lorenzo
authors.forename: Eiji
authors.initials: E
authors.lastname: Usui
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ueda
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Keiki
authors.initials: K
authors.lastname: Kawakami
authors.forename: Koji
authors.initials: K
authors.lastname: Oka
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Mitani
authors.forename: Takao
authors.initials: T
authors.lastname: Sekine
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Tamaki
authors.forename: Minoru
authors.initials: M
authors.lastname: Mizutani
authors.forename: Fumiharu
authors.initials: F
authors.lastname: Yagasaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Doki
authors.forename: Syuichi
authors.initials: S
authors.lastname: Miyawaki
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Katayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D050659:Core Binding Factor Alpha 1 Subunit; D050660:Core Binding Factors / Q000235:genetics; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D004802:Eosinophilia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D013577:Syndrome; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D050660:Core Binding Factors; D018076:DNA, Complementary; D015514:Oncogene Proteins, Fusion; D039221:mRNA Cleavage and Polyadenylation Factors; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta