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Erk negative feedback control enables pre-B cell transformation and represents a therapeutic target in acute lymphoblastic leukemia

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 r...

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Bibliographische Detailangaben
Hauptverfasser: Shojaee, Seyedmehdi (VerfasserIn) , Hofmann, Wolf-Karsten (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: June 11, 2015
In: Cancer cell
Year: 2015, Jahrgang: 28, Heft: 1, Pages: 114-128
ISSN:1878-3686
DOI:10.1016/j.ccell.2015.05.008
Online-Zugang:Verlag, teilw. kostenfrei, Volltext: http://dx.doi.org/10.1016/j.ccell.2015.05.008
Verlag, teilw. kostenfrei, Volltext: http://www.sciencedirect.com/science/article/pii/S1535610815001841
Volltext
Verfasserangaben:Seyedmehdi Shojaee, Rebecca Caeser, Maike Buchner, Eugene Park, Srividya Swaminathan, Christian Hurtz, Huimin Geng, Lai N. Chan, Lars Klemm, Wolf-Karsten Hofmann, Yi Hua Qiu, Nianxiang Zhang, Kevin R. Coombes, Elisabeth Paietta, Jeffery Molkentin, H. Phillip Koeffler, Cheryl L. Willman, Stephen P. Hunger, Ari Melnick, Steven M. Kornblau, and Markus Müschen
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 06.02.2018
Beschreibung:Online Resource
ISSN:1878-3686
DOI:10.1016/j.ccell.2015.05.008

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