We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Sp1/NFkappaB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemia.
- Authors
Liu, Shujun; Wu, Lai-Chu; Pang, Jiuxia; Santhanam, Ramasamy; Schwind, Sebastian; Wu, Yue-Zhong; Hickey, Christopher J; Yu, Jianhua; Becker, Heiko; Maharry, Kati; Radmacher, Michael D; Li, Chenglong; Whitman, Susan P; Mishra, Anjali; Stauffer, Nicole; Eiring, Anna M; Briesewitz, Roger; Baiocchi, Robert A; Chan, Kenneth K; Paschka, Peter; Caligiuri, Michael A; Byrd, John C; Croce, Carlo M; Bloomfield, Clara D; Perrotti, Danilo; Garzon, Ramiro; Marcucci, Guido
- Abstract
The biologic and clinical significance of KIT overexpression that associates with KIT gain-of-function mutations occurring in subsets of acute myeloid leukemia (AML) (i.e., core binding factor AML) is unknown. Here, we show that KIT mutations lead to MYC-dependent miR-29b repression and increased levels of the miR-29b target Sp1 in KIT-driven leukemia. Sp1 enhances its own expression by participating in a NFkappaB/HDAC complex that further represses miR-29b transcription. Upregulated Sp1 then binds NFkappaB and transactivates KIT. Therefore, activated KIT ultimately induces its own transcription. Our results provide evidence that the mechanisms of Sp1/NFkappaB/HDAC/miR-29b-dependent KIT overexpression contribute to leukemia growth and can be successfully targeted by pharmacological disruption of the Sp1/NFkappaB/HDAC complex or synthetic miR-29b treatment in KIT-driven AML.
- Publication
Cancer cell, 2010, Vol 17, Issue 4, p333
- ISSN
1878-3686
- Publication type
Journal Article
- DOI
10.1016/j.ccr.2010.03.008