Proteomic and genetic approaches identify Syk as an AML target.
Proteomic and genetic approaches identify Syk as an AML target.
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DOI：
10.1016/j.ccr.2009.08.018
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发表时间：
2009-10-06
期刊：
影响因子：
50.3
通讯作者：
Stegmaier K
中科院分区：
文献类型：
--
作者：
Hahn CK;Berchuck JE;Ross KN;Kakoza RM;Clauser K;Schinzel AC;Ross L;Galinsky I;Davis TN;Silver SJ;Root DE;Stone RM;DeAngelo DJ;Carroll M;Hahn WC;Carr SA;Golub TR;Kung AL;Stegmaier K
Cell-based screening can facilitate rapid identification of compounds inducing complex cellular phenotypes. Advancing a compound toward the clinic, however, generally requires identification of precise mechanisms of action. We previously found that epidermal growth factor receptor (EGFR) inhibitors induce acute myeloid leukemia (AML) differentiation via a non-EGFR mechanism. In this report, we integrated proteomic and RNAi-based strategies to identify their off-target anti-AML mechanism. These orthogonal approaches identified Syk as a target in AML. Genetic and pharmacological inactivation of Syk with a drug in clinical trial for other indications promoted differentiation of AML cells and attenuated leukemia growth in vivo. These results demonstrate the power of integrating diverse chemical, proteomic, and genomic screening approaches to identify therapeutic strategies for cancer.
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影响因子：
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作者：
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通讯作者：
Comb, MJ
影响因子：
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作者：
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DOI：
10.1124/jpet.106.109058
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