A Sleeping Beauty screen reveals NF-kB activation in CLL mouse model

作者：Zanesi Nicola; Balatti Veronica; Riordan Jesse; Burch Aaron; Rizzotto Lara; Palamarchuk Alexey; Cascione Luciano; Lagana Alessandro; Dupuy Adam J; Croce Carlo M; Pekarsky Yuri^*

来源：Blood, 2013, 121(21): 4355-4358.

DOI：10.1182/blood-2013-02-486035

TCL1 oncogene is overexpressed in aggressive form of human chronic lymphocytic leukemia (CLL) and its dysregulation in mouse B cells causes a CD5-positive leukemia similar to the aggressive form of human CLLs. To identify oncogenes that cooperate with Tcl1, we performed genetic screen in E mu-TCL1 mice using Sleeping Beauty transposon-mediated mutagenesis. Analysis of transposon common insertion sites identified 7 genes activated by transposon insertions. Overexpression of these genes in mouse CLL was confirmed by real time reverse transcription-polymerase chain re-action. Interestingly, the main known function of 4 of 7 genes (Nfkb1, Tab2, Map3K14, and Nfkbid) is participation in or activation of the nuclear factor-kB (NF-kB) pathway. In addition, activation of the NF-kB is 1 of main functions of Akt2, also identified in the screen. These findings demonstrate cooperation of Tcl1 and the NF-kB pathway in the pathogenesis of aggressive CLL. Identification cooperating cancer genes will result in the development of combinatorial therapies to treat CLL.

• 出版日期2013-5-23