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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Shojaee S,Caeser R,Buchner M,Park E,Swaminathan S,Hurtz C,Geng H,Chan LN,Klemm L,Hofmann WK,Qiu YH,Zhang N,Coombes KR,Paietta E,Molkentin J,Koeffler HP,Willman CL,Hunger SP,Melnick A,Kornblau SM,Müschen Mdoi
10.1016/j.ccell.2015.05.008subject
Has Abstractpub_date
2015-07-13 00:00:00pages
114-28issue
1eissn
1535-6108issn
1878-3686pii
S1535-6108(15)00184-1journal_volume
28pub_type
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