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FAK silencing inhibits leukemogenesis in BCR/ABL‐transformed hematopoietic cells
Author(s) -
Le Yi,
Xu Luhong,
Lu Jiayun,
Fang Jianpei,
Nardi Valentina,
Chai Li,
Silberstein Leslie E.
Publication year - 2009
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.21381
Subject(s) - small hairpin rna , cancer research , tyrosine kinase , gene silencing , abl , haematopoiesis , focal adhesion , cell growth , microbiology and biotechnology , signal transduction , biology , apoptosis , stem cell , gene knockdown , gene , biochemistry , genetics
Abstract Focal adhesion kinase (FAK) is constitutively activated and tyrosine phosphorylated in BCR/ABL‐transformed hematopoietic cells, but the role it plays during leukemogenesis remains unclear. Here, we examined the effects of RNA interference‐mediated FAK silencing on leukemogenesis induced by a BCR/ABL‐transformed cell line. Transduction of BCR/ABL‐BaF3 cells with FAK shRNA inhibited FAK expression and reduced STAT5 phosphorylation, but induced caspase‐3 activation. In vitro studies showed that treatment with FAK shRNA resulted in impaired cell proliferation and colony formation, while increasing cell apoptosis. Mice that received transplants of BCR/ABL‐BaF3 cells with FAK shRNA displayed significantly prolonged survival time and diminished leukemia progression. In addition, FAK silencing enhanced in vitro and in vivo efficacy of ABL tyrosine kinase inhibitor imatinib in BCR/ABL‐BaF3 cells. Our results suggest that FAK is critical for leukemogenesis and might be a potential target for leukemia therapy. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.