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Blood, 15 January 2006, Vol. 107, No. 2, pp. 781-785. Prepublished online as a Blood First Edition Paper on September 15, 2005; DOI 10.1182/blood-2005-06-2553. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 2005-06-2553v1 107/2/781    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by O'Neil, J. Articles by Look, A. T. Search for Related Content PubMed PubMed Citation Articles by O'Neil, J. Articles by Look, A. T. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief report Activating Notch1 mutations in mouse models of T-ALL Jennifer O'Neil, Jennifer Calvo, Keith McKenna, Veena Krishnamoorthy, Jon C. Aster, Craig H. Bassing, Frederick W. Alt, Michelle Kelliher, and A. Thomas Look From the Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA; Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Howard Hughes Medical Institute, The Children's Hospital, Department of Genetics, Harvard Medical School and The Center for Blood Research, Boston, MA. Recent studies have demonstrated that most patients with T-cell acute lymphocytic leukemia (T-ALL) have activating mutations in NOTCH1. We sought to determine whether these mutations are also acquired in mouse models of T-ALL. We sequenced the heterodimerization domain and the PEST domain of Notch1 in our mouse model of TAL1-induced leukemia and found that 74% of the tumors harbor activating mutations in Notch1. Cell lines derived from these tumors undergo G0/G1 arrest and apoptosis when treated with a -secretase inhibitor. In addition, we found activating Notch1 mutations in 31% of thymic lymphomas that occur in mice deficient for various combinations of the H2AX, Tp53, and Rag2 genes. Thus, Notch1 mutations are often acquired as a part of the molecular pathogenesis of T-ALLs that develop in mice with known predisposing genetic alterations. (Blood. 2006;107:781-785) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. J. Volanakis, R. T. Williams, and C. J. Sherr Stage-specific Arf tumor suppression in Notch1-induced T-cell acute lymphoblastic leukemia Blood, November 12, 2009; 114(20): 4451 - 4459. [Abstract] [Full Text] [PDF] 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] V. Asnafi, A. Buzyn, S. Le Noir, F. Baleydier, A. Simon, K. Beldjord, O. Reman, F. Witz, T. Fagot, E. Tavernier, et al. NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study Blood, April 23, 2009; 113(17): 3918 - 3924. [Abstract] [Full Text] [PDF] J. A. Bertout, S. A. Patel, B. H. Fryer, A. C. Durham, K. L. Covello, K. P. Olive, M. H. Goldschmidt, and M. C. Simon Heterozygosity for Hypoxia Inducible Factor 1{alpha} Decreases the Incidence of Thymic Lymphomas in a p53 Mutant Mouse Model Cancer Res., April 1, 2009; 69(7): 3213 - 3220. [Abstract] [Full Text] [PDF] I. Joshi, L. M. Minter, J. Telfer, R. M. Demarest, A. J. Capobianco, J. C. Aster, P. Sicinski, A. Fauq, T. E. Golde, and B. A. Osborne Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases Blood, February 19, 2009; 113(8): 1689 - 1698. [Abstract] [Full Text] [PDF] Y.-W. Kim, B.-K. Koo, H.-W. Jeong, M.-J. Yoon, R. Song, J. Shin, D.-C. Jeong, S.-H. Kim, and Y.-Y. Kong Defective Notch activation in microenvironment leads to myeloproliferative disease Blood, December 1, 2008; 112(12): 4628 - 4638. [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] K. L. Kathrein, S. Chari, and S. Winandy Ikaros Directly Represses the Notch Target Gene Hes1 in a Leukemia T Cell Line: IMPLICATIONS FOR CD4 REGULATION J. Biol. Chem., April 18, 2008; 283(16): 10476 - 10484. [Abstract] [Full Text] [PDF] K. De Keersmaecker, I. Lahortiga, N. Mentens, C. Folens, L. Van Neste, S. Bekaert, P. Vandenberghe, M. D. Odero, P. Marynen, and J. Cools In vitro validation of {gamma}-secretase inhibitors alone or in combination with other anti-cancer drugs for the treatment of T-cell acute lymphoblastic leukemia Haematologica, April 1, 2008; 93(4): 533 - 542. [Abstract] [Full Text] [PDF] S.-F. Wang, M. Aoki, Y. Nakashima, Y. Shinozuka, H. Tanaka, M. Taniwaki, M. Hattori, and N. Minato Development of Notch-dependent T-cell leukemia by deregulated Rap1 signaling Blood, March 1, 2008; 111(5): 2878 - 2886. [Abstract] [Full Text] [PDF] M. Eguchi-Ishimae, M. Eguchi, H. Kempski, and M. Greaves NOTCH1 mutation can be an early, prenatal genetic event in T-ALL Blood, January 1, 2008; 111(1): 376 - 378. [Abstract] [Full Text] [PDF] M. R. Mansour, V. Duke, L. Foroni, B. Patel, C. G. Allen, P. J. Ancliff, R. E. Gale, and D. C. Linch Notch-1 Mutations Are Secondary Events in Some Patients with T-Cell Acute Lymphoblastic Leukemia Clin. Cancer Res., December 1, 2007; 13(23): 6964 - 6969. [Abstract] [Full Text] [PDF] J. R. Gothert, R. L. Brake, M. Smeets, U. Duhrsen, C. G. Begley, and D. J. Izon NOTCH1 pathway activation is an early hallmark of SCL T leukemogenesis Blood, November 15, 2007; 110(10): 3753 - 3762. [Abstract] [Full Text] [PDF] S. Fischer, G. Mann, M. Konrad, M. Metzler, G. Ebetsberger, N. Jones, B. Nadel, O. Bodamer, O. A. Haas, K. Schmitt, et al. Screening for leukemia- and clone-specific markers at birth in children with T-cell precursor ALL suggests a predominantly postnatal origin Blood, October 15, 2007; 110(8): 3036 - 3038. [Abstract] [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] J. O'Neil, J. Grim, P. Strack, S. Rao, D. Tibbitts, C. Winter, J. Hardwick, M. Welcker, J. P. Meijerink, R. Pieters, et al. FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to {gamma}-secretase inhibitors J. Exp. Med., August 6, 2007; 204(8): 1813 - 1824. [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] V. Bolos, J. Grego-Bessa, and J. L. de la Pompa Notch Signaling in Development and Cancer Endocr. Rev., May 1, 2007; 28(3): 339 - 363. [Abstract] [Full Text] [PDF] I.-M. Shih and T.-L. Wang Notch Signaling, {gamma}-Secretase Inhibitors, and Cancer Therapy Cancer Res., March 1, 2007; 67(5): 1879 - 1882. [Abstract] [Full Text] [PDF] T. Palomero, W. K. Lim, D. T. Odom, M. L. Sulis, P. J. Real, A. Margolin, K. C. Barnes, J. O'Neil, D. Neuberg, A. P. Weng, et al. NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth PNAS, November 28, 2006; 103(48): 18261 - 18266. [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] M. Y. Chiang, M. L. Xu, G. Histen, O. Shestova, M. Roy, Y. Nam, S. C. Blacklow, D. B. Sacks, W. S. Pear, and J. C. Aster Identification of a Conserved Negative Regulatory Sequence That Influences the Leukemogenic Activity of NOTCH1. Mol. Cell. Biol., August 1, 2006; 26(16): 6261 - 6271. [Abstract] [Full Text] [PDF] A. P. Weng, J. M. Millholland, Y. Yashiro-Ohtani, M. L. Arcangeli, A. Lau, C. Wai, C. del Bianco, C. G. Rodriguez, H. Sai, J. Tobias, et al. c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma Genes & Dev., August 1, 2006; 20(15): 2096 - 2109. [Abstract] [Full Text] [PDF] E. J. Reschly, C. Spaulding, T. Vilimas, W. V. Graham, R. L. Brumbaugh, I. Aifantis, W. S. Pear, and B. L. Kee Notch1 promotes survival of E2A-deficient T cell lymphomas through pre-T cell receptor-dependent and -independent mechanisms Blood, May 15, 2006; 107(10): 4115 - 4121. [Abstract] [Full Text] [PDF] K. G. Leong and A. Karsan Recent insights into the role of Notch signaling in tumorigenesis Blood, March 15, 2006; 107(6): 2223 - 2233. [Abstract] [Full Text] [PDF]

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