|
|
Blood, 15 May 2006, Vol. 107, No. 10, pp. 4115-4121.
Prepublished online as a Blood First Edition Paper on January 31, 2006; DOI 10.1182/blood-2005-09-3551.
 Previous Article | Next Article 
Submitted September 7, 2005
Accepted January 13, 2006
Notch1 promotes survival of E2A-deficient T cell lymphomas through Pre-T cell receptor dependent and independent mechanisms
Erica J Reschly, Christina Spaulding, Tomas Vilimas, W Vallen Graham, Rachel L Brumbaugh, Iannis Aifantis, Warren S Pear, and Barbara L Kee*
Departments of Pathology, University of Chicago, Chicago, IL, USA; Committees on Cancer Biology, University of Chicago, Chicago, IL, USA
Departments of Pathology, University of Chicago, Chicago, IL, USA
Departments of Medicine, University of Chicago, Chicago, IL, USA
Departments of Medicine, University of Chicago, Chicago, IL, USA; Committees on Immunology, University of Chicago, Chicago, IL, USA; Committees on Cancer Biology, University of Chicago, Chicago, IL, USA
Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA
Departments of Pathology, University of Chicago, Chicago, IL, USA; Committees on Immunology, University of Chicago, Chicago, IL, USA; Committees on Cancer Biology, University of Chicago, Chicago, IL, USA
* Corresponding author; email: bkee{at}bsd.uchicago.edu.
Loss of E2A transcription factor activity or activation of the intracellular form of Notch1 (ICN) leads to development of leukemia or lymphoma in humans or mice respectively. Current models propose that ICN functions by suppressing E2A though a pre-T cell receptor (TCR) dependent mechanism. Here we show that lymphomas arising in E2A -/- mice require activation of Notch1 for their survival and have accumulated mutations in, or near, the Notch1 PEST domain resulting in increased stability and signaling. In contrast, lymphomas arising in p53-/- mice show activation of Notch1 but no mutations were identified in ICN. The requirement for Notch1 signaling in E2A-/- lymphomas cannot be overcome by ectopic expression of pT ; however, pT is required for optimal survival and expansion of these cells. Our findings indicate that activation of Notch1 is an important "second hit" for transformation of E2A-/- T cell lymphomas and that Notch1 promotes survival through both pre-TCR dependent and independent mechanisms.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
K. Cullion, K. M. Draheim, N. Hermance, J. Tammam, V. M. Sharma, C. Ware, G. Nikov, V. Krishnamoorthy, P. K. Majumder, and M. A. Kelliher
Targeting the Notch1 and mTOR pathways in a mouse T-ALL model
Blood,
June 11, 2009;
113(24):
6172 - 6181.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kindler, M. G. Cornejo, C. Scholl, J. Liu, D. S. Leeman, J. E. Haydu, S. Frohling, B. H. Lee, and D. G. Gilliland
K-RasG12D-induced T-cell lymphoblastic lymphoma/leukemias harbor Notch1 mutations and are sensitive to {gamma}-secretase inhibitors
Blood,
October 15, 2008;
112(8):
3373 - 3382.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Xu, Q. Yu, R. Subrahmanyam, M. J. Difilippantonio, T. Ried, and J. M. Sen
{beta}-Catenin Expression Results in p53-Independent DNA Damage and Oncogene-Induced Senescence in Prelymphomagenic Thymocytes In Vivo
Mol. Cell. Biol.,
March 1, 2008;
28(5):
1713 - 1723.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Bessette, M. L. Lang, R. A. Fava, M. Grundy, J. Heinen, L. Horne, R. Spolski, A. Al-Shami, H. C. Morse III, W. J. Leonard, et al.
A Stat5b transgene is capable of inducing CD8+ lymphoblastic lymphoma in the absence of normal TCR/MHC signaling
Blood,
January 1, 2008;
111(1):
344 - 350.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Gounari and M. Dose
Lef-1: NOTCHed up in T-cell lymphomas
Blood,
October 1, 2007;
110(7):
2227 - 2227.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Fasseu, P. D. Aplan, M. Chopin, N. Boissel, J.-C. Bories, J. Soulier, H. von Boehmer, F. Sigaux, and A. Regnault
p16INK4A tumor suppressor gene expression and CD3{epsilon} deficiency but not pre-TCR deficiency inhibit TAL1-linked T-lineage leukemogenesis
Blood,
October 1, 2007;
110(7):
2610 - 2619.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Spaulding, E. J. Reschly, D. E. Zagort, Y. Yashiro-Ohtani, L. J. Beverly, A. Capobianco, W. S. Pear, and B. L. Kee
Notch1 co-opts lymphoid enhancer factor 1 for survival of murine T-cell lymphomas
Blood,
October 1, 2007;
110(7):
2650 - 2658.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Thompson, S. Buonamici, M. L. Sulis, T. Palomero, T. Vilimas, G. Basso, A. Ferrando, and I. Aifantis
The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia
J. Exp. Med.,
August 6, 2007;
204(8):
1825 - 1835.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Chan, A. P. Weng, R. Tibshirani, J. C. Aster, and P. J. Utz
Notch signals positively regulate activity of the mTOR pathway in T-cell acute lymphoblastic leukemia
Blood,
July 1, 2007;
110(1):
278 - 286.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Guo, M. Dose, D. Kovalovsky, R. Chang, J. O'Neil, A. T. Look, H. von Boehmer, K. Khazaie, and F. Gounari
{beta}-Catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation
Blood,
June 15, 2007;
109(12):
5463 - 5472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Xu and B. L. Kee
Growth factor independent 1B (Gfi1b) is an E2A target gene that modulates Gata3 in T-cell lymphomas
Blood,
May 15, 2007;
109(10):
4406 - 4414.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. M. Sharma, J. A. Calvo, K. M. Draheim, L. A. Cunningham, N. Hermance, L. Beverly, V. Krishnamoorthy, M. Bhasin, A. J. Capobianco, and M. A. Kelliher
Notch1 Contributes to Mouse T-Cell Leukemia by Directly Inducing the Expression of c-myc
Mol. Cell. Biol.,
November 1, 2006;
26(21):
8022 - 8031.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
