| First Author | Zanesi N | Year | 2013 |
| Journal | Blood | Volume | 121 |
| Issue | 21 | Pages | 4355-8 |
| PubMed ID | 23591791 | Mgi Jnum | J:198462 |
| Mgi Id | MGI:5496765 | Doi | 10.1182/blood-2013-02-486035 |
| Citation | Zanesi N, et al. (2013) A Sleeping Beauty screen reveals NF-kB activation in CLL mouse model. Blood 121(21):4355-8 |
| abstractText | 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 Emu-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. |
