Cools Jan, Quentmeier Hilmar, Huntly Brian J P, Marynen Peter, Griffin James D, Drexler Hans G, Gilliland D Gary
Division of Hematology and the Howard Hughes Medical Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Blood. 2004 Apr 1;103(7):2802-5. doi: 10.1182/blood-2003-07-2479. Epub 2003 Nov 20.
We recently identified the chimeric kinase FIP1L1-platelet-derived growth factor receptor alpha (PDGFRalpha) as a cause of the hypereosinophilic syndrome and of chronic eosinophilic leukemia. To investigate the role of FIP1L1-PDGFRA in the pathogenesis of acute leukemia, we screened 87 leukemia cell lines for the presence of FIP1L1-PDGFRA. One cell line, EOL-1, expressed the FIP1L1-PDGFRA fusion. Three structurally divergent kinase inhibitors--imatinib (STI-571), PKC412, and SU5614--inhibited the growth of EOL-1 cells. These results indicate that the fusion of FIP1L1 to PDGFRA occurs rarely in leukemia cell lines, but they identify EOL-1 as an in vitro model for the study of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia and for the analysis of small molecule inhibitors of FIP1L1-PDGFRalpha.
我们最近鉴定出嵌合激酶FIP1L1-血小板衍生生长因子受体α(PDGFRα)是嗜酸性粒细胞增多综合征和慢性嗜酸性粒细胞白血病的病因。为了研究FIP1L1-PDGFRA在急性白血病发病机制中的作用,我们在87株白血病细胞系中筛查FIP1L1-PDGFRA的存在情况。一株细胞系EOL-1表达FIP1L1-PDGFRA融合基因。三种结构不同的激酶抑制剂——伊马替尼(STI-571)、PKC412和SU5614——抑制EOL-1细胞的生长。这些结果表明FIP1L1与PDGFRA的融合在白血病细胞系中很少发生,但它们确定EOL-1为研究FIP1L1-PDGFRA阳性慢性嗜酸性粒细胞白血病以及分析FIP1L1-PDGFRα小分子抑制剂的体外模型。