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Acute lymphocytic leukemia pediatric rct

Parham Ramezani-Rad, Huimin Geng, Christian Hurtz, Lai N Chan, Zhengshan Chen, Hassan Jumaa, Ari Melnick, Elisabeth Paietta, William L Carroll, Cheryl L Willman, Véronique Lefebvre, Markus Müschen
The Sox4 transcription factor mediates early B-cell differentiation. Compared with normal pre-B cells, SOX4 promoter regions in Ph(+) ALL cells are significantly hypomethylated. Loss and gain-of-function experiments identified Sox4 as a critical activator of PI3K/AKT and MAPK signaling in ALL cells. ChIP experiments confirmed that SOX4 binds to and transcriptionally activates promoters of multiple components within the PI3K/AKT and MAPK signaling pathways. Cre-mediated deletion of Sox4 had little effect on normal pre-B cells but compromised proliferation and viability of leukemia cells, which was rescued by BCL2L1 and constitutively active AKT and p110 PI3K...
January 3, 2013: Blood
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