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

Nicola Zanesi, Veronica Balatti, Jesse Riordan, Aaron Burch, Lara Rizzotto, Alexey Palamarchuk, Luciano Cascione, Alessandro Lagana, Adam J. Dupuy, Carlo M. Croce, Yuri Pekarsky

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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 Eμ-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 reaction. 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.

Original languageEnglish
Pages (from-to)4355-4358
Number of pages4
JournalBlood
Volume121
Issue number21
DOIs
StatePublished - 23 May 2013
Externally publishedYes

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