In Vivo RNAi screening identifies a leukemia-specific dependence on integrin beta 3 signaling.
In Vivo RNAi screening identifies a leukemia-specific dependence on integrin beta 3 signaling.
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DOI：
10.1016/j.ccr.2013.05.004
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发表时间：
2013-07-08
期刊：
影响因子：
50.3
通讯作者：
Ebert BL
中科院分区：
文献类型：
--
作者：
Miller PG;Al-Shahrour F;Hartwell KA;Chu LP;Järås M;Puram RV;Puissant A;Callahan KP;Ashton J;McConkey ME;Poveromo LP;Cowley GS;Kharas MG;Labelle M;Shterental S;Fujisaki J;Silberstein L;Alexe G;Al-Hajj MA;Shelton CA;Armstrong SA;Root DE;Scadden DT;Hynes RO;Mukherjee S;Stegmaier K;Jordan CT;Ebert BL
We used an in vivo short hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo, and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase, Syk. In contrast, loss of Itgb3 in normal HSPCs did not affect engraftment, reconstitution, or differentiation. Finally, we confirmed that Itgb3 is dispensable for normal hematopoiesis and required for leukemogenesis using an Itgb3 knockout mouse model. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML.
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影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
影响因子：
15.9
作者：
Hodivala-Dilke, KM;McHugh, KP;Hynes, RO
通讯作者：
Hynes, RO
DOI：
10.1124/jpet.106.109058
发表时间：
2006-12-01
影响因子：
3.5
作者：
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通讯作者：
Masuda, Esteban S.
影响因子：
20.3
作者：
Guzman, ML;Rossi, RM;Jordan, CT
通讯作者：
Jordan, CT
影响因子：
64.8
作者：
Bild, AH;Yao, G;Nevins, JR
通讯作者：
Nevins, JR