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Molecular analysis of PDGFR α / β genes in core binding factor leukemia with eosinophilia
Author(s) -
Monma Fumihiko,
Nishii Kazuhiro,
Lorenzo Felipe,
Usui Eiji,
Ueda Yuichiro,
Watanabe Yasuyuki,
Kawakami Keiki,
Oka Koji,
Mitani Hidetsugu,
Sekine Takao,
Tamaki Shigehisa,
Mizutani Minoru,
Yagasaki Fumiharu,
Doki Noriko,
Miyawaki Syuichi,
Katayama Naoyuki,
Shiku Hiroshi
Publication year - 2006
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2005.00543.x
Subject(s) - core binding factor , cancer research , fusion gene , myeloid leukemia , eosinophilia , tyrosine kinase , leukemia , biology , platelet derived growth factor receptor , gene , immunology , transcription factor , genetics , growth factor , signal transduction , receptor
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 ( PDGFR α ), is found in idiopathic hypereosinophilic syndrome. The involvement of another chimeric gene, PDGFR β , 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‐PDGFR α fusion gene and for mutations in the juxtamembrane and tyrosine kinase domains of PDGFR α / β genes in 22 cases of CBF leukemia with eosinophilia. Among these cases, no FIP1L1‐PDGFR α fusion gene was found. Although cDNA sequencing also detected three types of single‐nucleotide alterations at kinase domains in PDGFR α / β genes, all of them were silent changes and polymorphisms. Therefore, PDGFR α / β genes do not appear to play a significant pathogenetic role in eosinophilia or leukemogenesis of CBF leukemia.