Perturbation of Ikaros isoform selection by MLV integration is a cooperative event in NotchIC-induced T cell leukemogenesis

Levi J. Beverly, Anthony J Capobianco

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

The chromosomal translocation t(7;9)(q34;q34.3) in human T cell acute lymphoblastic leukemia (T-ALL) results in the aberrant expression of the intracellular domain of Notch (Nic). Consistent with the current multistep model for tumorigenesis, mice that express Nic in T cell progenitors develop a T-ALL-like disease with a lengthened latency. Proviral insertional mutagenesis greatly accelerated the onset of leukemia in Nic transgenic mice. We demonstrate that the Ikaros (Ik) locus is a common target of proviral integration in Nic transgenic mice, which results in the loss of Ik DNA binding activity through altered isoform expression. We propose that cooperative leukemogenesis occurs in cells that have constitutive Nic and altered Ik isoform expression because genes normally repressed by Ik become activated by Nic/CSL.

Original languageEnglish
Pages (from-to)551-564
Number of pages14
JournalCancer Cell
Volume3
Issue number6
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

Fingerprint

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Transgenic Mice
Protein Isoforms
T-Lymphocytes
Genetic Translocation
Insertional Mutagenesis
Carcinogenesis
Leukemia
Gene Expression
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Perturbation of Ikaros isoform selection by MLV integration is a cooperative event in NotchIC-induced T cell leukemogenesis. / Beverly, Levi J.; Capobianco, Anthony J.

In: Cancer Cell, Vol. 3, No. 6, 01.06.2003, p. 551-564.

Research output: Contribution to journalArticle

@article{3eff567c6b5a4074a8a46df47971b413,
title = "Perturbation of Ikaros isoform selection by MLV integration is a cooperative event in NotchIC-induced T cell leukemogenesis",
abstract = "The chromosomal translocation t(7;9)(q34;q34.3) in human T cell acute lymphoblastic leukemia (T-ALL) results in the aberrant expression of the intracellular domain of Notch (Nic). Consistent with the current multistep model for tumorigenesis, mice that express Nic in T cell progenitors develop a T-ALL-like disease with a lengthened latency. Proviral insertional mutagenesis greatly accelerated the onset of leukemia in Nic transgenic mice. We demonstrate that the Ikaros (Ik) locus is a common target of proviral integration in Nic transgenic mice, which results in the loss of Ik DNA binding activity through altered isoform expression. We propose that cooperative leukemogenesis occurs in cells that have constitutive Nic and altered Ik isoform expression because genes normally repressed by Ik become activated by Nic/CSL.",
author = "Beverly, {Levi J.} and Capobianco, {Anthony J}",
year = "2003",
month = "6",
day = "1",
doi = "10.1016/S1535-6108(03)00137-5",
language = "English",
volume = "3",
pages = "551--564",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - Perturbation of Ikaros isoform selection by MLV integration is a cooperative event in NotchIC-induced T cell leukemogenesis

AU - Beverly, Levi J.

AU - Capobianco, Anthony J

PY - 2003/6/1

Y1 - 2003/6/1

N2 - The chromosomal translocation t(7;9)(q34;q34.3) in human T cell acute lymphoblastic leukemia (T-ALL) results in the aberrant expression of the intracellular domain of Notch (Nic). Consistent with the current multistep model for tumorigenesis, mice that express Nic in T cell progenitors develop a T-ALL-like disease with a lengthened latency. Proviral insertional mutagenesis greatly accelerated the onset of leukemia in Nic transgenic mice. We demonstrate that the Ikaros (Ik) locus is a common target of proviral integration in Nic transgenic mice, which results in the loss of Ik DNA binding activity through altered isoform expression. We propose that cooperative leukemogenesis occurs in cells that have constitutive Nic and altered Ik isoform expression because genes normally repressed by Ik become activated by Nic/CSL.

AB - The chromosomal translocation t(7;9)(q34;q34.3) in human T cell acute lymphoblastic leukemia (T-ALL) results in the aberrant expression of the intracellular domain of Notch (Nic). Consistent with the current multistep model for tumorigenesis, mice that express Nic in T cell progenitors develop a T-ALL-like disease with a lengthened latency. Proviral insertional mutagenesis greatly accelerated the onset of leukemia in Nic transgenic mice. We demonstrate that the Ikaros (Ik) locus is a common target of proviral integration in Nic transgenic mice, which results in the loss of Ik DNA binding activity through altered isoform expression. We propose that cooperative leukemogenesis occurs in cells that have constitutive Nic and altered Ik isoform expression because genes normally repressed by Ik become activated by Nic/CSL.

UR - http://www.scopus.com/inward/record.url?scp=0037710256&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037710256&partnerID=8YFLogxK

U2 - 10.1016/S1535-6108(03)00137-5

DO - 10.1016/S1535-6108(03)00137-5

M3 - Article

C2 - 12842084

AN - SCOPUS:0037710256

VL - 3

SP - 551

EP - 564

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 6

ER -