Journal article
A Sleeping Beauty screen reveals NF-kB activation in CLL mouse model
Blood, Vol.121(21), pp.4355-4358
05/23/2013
DOI: 10.1182/blood-2013-02-486035
PMCID: PMC3663428
PMID: 23591791
Abstract
Tcl1 cooperates with the NF-kB pathway in the pathogenesis of the aggressive form of CLL.
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.
Details
- Title: Subtitle
- A Sleeping Beauty screen reveals NF-kB activation in CLL mouse model
- Creators
- Nicola Zanesi - Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OHVeronica Balatti - Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OHJesse Riordan - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA; andAaron Burch - Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OHLara Rizzotto - Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OHAlexey Palamarchuk - Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OHLuciano Cascione - Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OHAlessandro Lagana - Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OHAdam J Dupuy - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA; andCarlo M Croce - Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OHYuri Pekarsky - Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OH
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.121(21), pp.4355-4358
- Publisher
- American Society of Hematology; Washington, DC
- DOI
- 10.1182/blood-2013-02-486035
- PMID
- 23591791
- PMCID
- PMC3663428
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Grant note
- P01-CA81534 / National Institutes of Health
- Language
- English
- Date published
- 05/23/2013
- Academic Unit
- Anatomy and Cell Biology; Pathology
- Record Identifier
- 9984025441002771
Metrics
30 Record Views