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

doi:10.1182/blood-2013-02-486035

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 journal › Article › peer-review

28 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 language	English
Pages (from-to)	4355-4358
Number of pages	4
Journal	Blood
Volume	121
Issue number	21
DOIs	https://doi.org/10.1182/blood-2013-02-486035
State	Published - 23 May 2013
Externally published	Yes

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@article{5e8811da2464435890276cc9af7d7df0,

title = "A Sleeping Beauty screen reveals NF-kB activation in CLL mouse model",

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.",

author = "Nicola Zanesi and Veronica Balatti and Jesse Riordan and Aaron Burch and Lara Rizzotto and Alexey Palamarchuk and Luciano Cascione and Alessandro Lagana and Dupuy, \{Adam J.\} and Croce, \{Carlo M.\} and Yuri Pekarsky",

note = "Publisher Copyright: {\textcopyright} 2013 by The American Society of Hematology.",

year = "2013",

month = may,

day = "23",

doi = "10.1182/blood-2013-02-486035",

language = "English",

volume = "121",

pages = "4355--4358",

journal = "Blood",

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T1 - A Sleeping Beauty screen reveals NF-kB activation in CLL mouse model

AU - Zanesi, Nicola

AU - Balatti, Veronica

AU - Riordan, Jesse

AU - Burch, Aaron

AU - Rizzotto, Lara

AU - Palamarchuk, Alexey

AU - Cascione, Luciano

AU - Lagana, Alessandro

AU - Dupuy, Adam J.

AU - Croce, Carlo M.

AU - Pekarsky, Yuri

PY - 2013/5/23

Y1 - 2013/5/23

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84880420282

U2 - 10.1182/blood-2013-02-486035

DO - 10.1182/blood-2013-02-486035

M3 - Article

C2 - 23591791

AN - SCOPUS:84880420282

SN - 0006-4971

VL - 121

SP - 4355

EP - 4358

JO - Blood

JF - Blood

IS - 21

ER -

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

Abstract

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