| Literature DB >> 26073130 |
Seyedmehdi Shojaee1, Rebecca Caeser2, Maike Buchner1, Eugene Park3, Srividya Swaminathan1, Christian Hurtz1, Huimin Geng1, Lai N Chan1, Lars Klemm1, Wolf-Karsten Hofmann4, Yi Hua Qiu5, Nianxiang Zhang6, Kevin R Coombes6, Elisabeth Paietta7, Jeffery Molkentin8, H Phillip Koeffler9, Cheryl L Willman10, Stephen P Hunger11, Ari Melnick12, Steven M Kornblau5, Markus Müschen13.
Abstract
Studying mechanisms of malignant transformation of human pre-B cells, we found that acute activation of oncogenes induced immediate cell death in the vast majority of cells. Few surviving pre-B cell clones had acquired permissiveness to oncogenic signaling by strong activation of negative feedback regulation of Erk signaling. Studying negative feedback regulation of Erk in genetic experiments at three different levels, we found that Spry2, Dusp6, and Etv5 were essential for oncogenic transformation in mouse models for pre-B acute lymphoblastic leukemia (ALL). Interestingly, a small molecule inhibitor of DUSP6 selectively induced cell death in patient-derived pre-B ALL cells and overcame conventional mechanisms of drug-resistance.Entities:
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Year: 2015 PMID： 26073130 PMCID： PMC4565502 DOI： 10.1016/j.ccell.2015.05.008
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743