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Publication : Growth factor independence 1 antagonizes a p53-induced DNA damage response pathway in lymphoblastic leukemia.

First Author  Khandanpour C Year  2013
Journal  Cancer Cell Volume  23
Issue  2 Pages  200-14
PubMed ID  23410974 Mgi Jnum  J:194309
Mgi Id  MGI:5473425 Doi  10.1016/j.ccr.2013.01.011
Citation  Khandanpour C, et al. (2013) Growth factor independence 1 antagonizes a p53-induced DNA damage response pathway in lymphoblastic leukemia. Cancer Cell 23(2):200-14
abstractText  Most patients with acute lymphoblastic leukemia (ALL) fail current treatments highlighting the need for better therapies. Because oncogenic signaling activates a p53-dependent DNA damage response and apoptosis, leukemic cells must devise appropriate countermeasures. We show here that growth factor independence 1 (Gfi1) can serve such a function because Gfi1 ablation exacerbates p53 responses and lowers the threshold for p53-induced cell death. Specifically, Gfi1 restricts p53 activity and expression of proapoptotic p53 targets such as Bax, Noxa (Pmaip1), and Puma (Bbc3). Subsequently, Gfi1 ablation cures mice from leukemia and limits the expansion of primary human T-ALL xenografts in mice. This suggests that targeting Gfi1 could improve the prognosis of patients with T-ALL or other lymphoid leukemias.
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