Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2137286 | Leukemia Research | 2011 | 7 Pages |
Abstract
KIT mutations may be associated with a poor prognosis in t(8;21) AML. Heat shock protein 90 (Hsp90) is a molecular chaperone frequently used by cancer cells to stabilize mutant oncoproteins. Inhibition of Hsp90 by 17-allylamino-17-demethoxygeldanamycin (17-AAG) disrupted downstream signaling pathways of mutant KIT in Kasumi-1 cells. AML1-ETO fusion gene and mutated KIT act as “two-hit” factors in Kasumi-1 cells. Histone deacetylation (HDAC) inhibitors sodium phenylbutyrate (PB) and valproic acid (VPA) block AML1-ETO. Co-treatment with 17-AAG and PB or 17-AAG and VPA resulted in a synergistic effect in Kasumi-1 cells. Our results confirmed that Hsp90 and mutated KIT were valid molecular targets in the therapy of AML.
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Authors
Wenjuan Yu, Jianxiang Wang, Jie Jin, Wenbin Qian, Jiejing Qian, Yizhi Cheng, Lei Wang,