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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2540-2543. Prepublished online as a Blood First Edition Paper on November 10, 2005; DOI 10.1182/blood-2005-07-3013. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-07-3013v1 107/6/2540    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 Lin, Y.-W. Articles by Aplan, P. D. Search for Related Content PubMed PubMed Citation Articles by Lin, Y.-W. Articles by Aplan, P. D. Related Collections Hematopoiesis and Stem Cells Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief report Notch1 mutations are important for leukemic transformation in murine models of precursor-T leukemia/lymphoma Ying-Wei Lin, Rebecca A. Nichols, John J. Letterio, and Peter D. Aplan From the Genetics Branch and Laboratory for Cell Regulation and Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. NOTCH1 is frequently mutated in human precursor T-cell lymphoblastic leukemia/lymphoma (pre-T LBL). In the current study, we found that 13 of 19 cell lines and 29 of 49 primary tumors from SCL/LMO1, OLIG2/LMO1, OLIG2, LMO1, NUP98/HOXD13, and p27-/-/SMAD3+/- mice had Notch1 mutations in either the heterodimerization (HD) or the glutamic acid/serine/threonine (PEST) domain but not both. Thymocytes from clinically healthy SCL/LMO1 mice aged 5 weeks did not have Notch1 mutations, whereas thymocytes from clinically healthy SCL/LMO1 mice aged 8 to 12 weeks did have Notch1 mutations and formed tumors upon transplantation into nude mice. Remarkably, all of the HD domain mutations that we identified were single-base substitutions, whereas all of the PEST domain mutations were insertions or deletions, half of which mapped to 1 of 2 mutational "hot spots." Taken together, these findings indicate that Notch1 mutations are very frequent events that are acquired relatively early in the process of leukemic transformation and are important for leukemic cell growth. (Blood. 2006;107: 2540-2543) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. D. Baldus, J. Thibaut, N. Goekbuget, A. Stroux, C. Schlee, M. Mossner, T. Burmeister, S. Schwartz, C. D. Bloomfield, D. Hoelzer, et al. 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A. Kefas, L. D. Comeau, M. P. Hawkinson, Q. Su, Y. Kotliarov, J. Lee, W. Zhang, et al. Notch-1 regulates transcription of the epidermal growth factor receptor through p53 Carcinogenesis, May 1, 2008; 29(5): 918 - 925. [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] 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. 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[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]

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