Separation of Notch1 Promoted Lineage Commitment and Expansion/Transformation in Developing T Cells

doi:10.1084/jem.194.1.99

Published online 2 July 2001. doi:10.1084/jem.194.1.99

This Article

	Full Text
	Full Text (PDF, 164K)
	PPT slides of all figures
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Allman, D.
	Articles by Pear, W. S.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Allman, D.
	Articles by Pear, W. S.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0022-1007/2001/7/99/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 1, July 2, 2001 99-106

Brief Definitive Report

Separation of Notch1 Promoted Lineage Commitment and Expansion/Transformation in Developing T Cells

David Allman^a^,c, Fredrick G. Karnell^a^,b, Jennifer A. Punt^d, Sonia Bakkour^a^,b, Lanwei Xu^a^,b, Peggy Myung^c, Gary A. Koretzky^a^,c, John C. Pui^a^,b, Jon C. Aster^e, and Warren S. Pear^a^,b

^a Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 19104
^b Institute of Medicine and Engineering, University of Pennsylvania Medical Center, Philadelphia, PA 19104
^c Abramson Family Cancer Research Institute, University of Pennsylvania Medical Center, Philadelphia, PA 19104
^d Department of Biology, Haverford College, Haverford, PA 19041
^e Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115
611 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104-6160.215-573-8606215-573-7764

wpear{at}mail.med.upenn.edu

Notch1 signaling is required for T cell development. We havepreviously demonstrated that expression of a dominant activeNotch1 (ICN1) transgene in hematopoietic stem cells (HSCs) leadsto thymic-independent development of CD4⁺CD8⁺ double-positive(DP) T cells in the bone marrow (BM). To understand the functionof Notch1 in early stages of T cell development, we assessedthe ability of ICN1 to induce extrathymic T lineage commitmentin BM progenitors from mice that varied in their capacity toform a functional pre-T cell receptor (TCR). Whereas mice repopulatedwith ICN1 transduced HSCs from either recombinase deficient(Rag-2^–/–) or Src homology 2 domain–containingleukocyte protein of 76 kD (SLP-76)^–/– mice failedto develop DP BM cells, recipients of ICN1-transduced Rag-2^–/–progenitors contained two novel BM cell populations indicativeof pre-DP T cell development. These novel BM populations arecharacterized by their expression of CD3 ${varepsilon}$ and pre-T ${alpha}$ mRNA andthe surface proteins CD44 and CD25. In contrast, complementationof Rag-2^–/– mice with a TCRβ transgene restoredICN1-induced DP development in the BM within 3 wk after BM transfer(BMT). At later time points, this population selectively andconsistently gave rise to T cell leukemia. These findings demonstratethat Notch signaling directs T lineage commitment from multipotentprogenitor cells; however, both expansion and leukemic transformationof this population are dependent on T cell–specific signalsassociated with development of DP thymocytes.

Key Words: leukemia • development • hematopoiesis • lymphocyte • stem cells

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Volanakis, E. J., Williams, R. T., Sherr, C. J. (2009). Stage-specific Arf tumor suppression in Notch1-induced T-cell acute lymphoblastic leukemia. Blood 114: 4451-4459 [Abstract] [Full Text]
Asnafi, V., Buzyn, A., Le Noir, S., Baleydier, F., Simon, A., Beldjord, K., Reman, O., Witz, F., Fagot, T., Tavernier, E., Turlure, P., Leguay, T., Huguet, F., Vernant, J.-P., Daniel, F., Bene, M.-C., Ifrah, N., Thomas, X., Dombret, H., Macintyre, E. (2009). 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 113: 3918-3924 [Abstract] [Full Text]
Kleinmann, E., Geimer Le Lay, A.-S., Sellars, M., Kastner, P., Chan, S. (2008). Ikaros Represses the Transcriptional Response to Notch Signaling in T-Cell Development. Mol. Cell. Biol. 28: 7465-7475 [Abstract] [Full Text]
Wang, S.-F., Aoki, M., Nakashima, Y., Shinozuka, Y., Tanaka, H., Taniwaki, M., Hattori, M., Minato, N. (2008). Development of Notch-dependent T-cell leukemia by deregulated Rap1 signaling. Blood 111: 2878-2886 [Abstract] [Full Text]
Michie, A. M., Chan, A. C., Ciofani, M., Carleton, M., Lefebvre, J. M., He, Y., Allman, D. M., Wiest, D. L., Zuniga-Pflucker, J. C., Izon, D. J. (2007). Constitutive Notch signalling promotes CD4 CD8 thymocyte differentiation in the absence of the pre-TCR complex, by mimicking pre-TCR signals. Int Immunol 19: 1421-1430 [Abstract] [Full Text]
Gothert, J. R., Brake, R. L., Smeets, M., Duhrsen, U., Begley, C. G., Izon, D. J. (2007). NOTCH1 pathway activation is an early hallmark of SCL T leukemogenesis. Blood 110: 3753-3762 [Abstract] [Full Text]
Spaulding, C., Reschly, E. J., Zagort, D. E., Yashiro-Ohtani, Y., Beverly, L. J., Capobianco, A., Pear, W. S., Kee, B. L. (2007). Notch1 co-opts lymphoid enhancer factor 1 for survival of murine T-cell lymphomas. Blood 110: 2650-2658 [Abstract] [Full Text]
Guidos, C. J. (2006). Synergy between the pre-T cell receptor and Notch: cementing the {alpha}{beta} lineage choice. JEM 203: 2233-2237 [Abstract] [Full Text]
Chiang, M. Y., Xu, M. L., Histen, G., Shestova, O., Roy, M., Nam, Y., Blacklow, S. C., Sacks, D. B., Pear, W. S., Aster, J. C. (2006). Identification of a Conserved Negative Regulatory Sequence That Influences the Leukemogenic Activity of NOTCH1. Mol. Cell. Biol. 26: 6261-6271 [Abstract] [Full Text]
Campese, A. F., Garbe, A. I., Zhang, F., Grassi, F., Screpanti, I., von Boehmer, H. (2006). Notch1-dependent lymphomagenesis is assisted by but does not essentially require pre-TCR signaling. Blood 108: 305-310 [Abstract] [Full Text]
Reschly, E. J., Spaulding, C., Vilimas, T., Graham, W. V., Brumbaugh, R. L., Aifantis, I., Pear, W. S., Kee, B. L. (2006). Notch1 promotes survival of E2A-deficient T cell lymphomas through pre-T cell receptor-dependent and -independent mechanisms. Blood 107: 4115-4121 [Abstract] [Full Text]
Leong, K. G., Karsan, A. (2006). Recent insights into the role of Notch signaling in tumorigenesis. Blood 107: 2223-2233 [Abstract] [Full Text]
Borghesi, L., Aites, J., Nelson, S., Lefterov, P., James, P., Gerstein, R. (2005). E47 is required for V(D)J recombinase activity in common lymphoid progenitors. JEM 202: 1669-1677 [Abstract] [Full Text]
Garcia-Ojeda, M. E., Dejbakhsh-Jones, S., Chatterjea-Matthes, D., Mukhopadhyay, A., BitMansour, A., Weissman, I. L., Brown, J. M. Y., Strober, S. (2005). Stepwise Development of Committed Progenitors in the Bone Marrow That Generate Functional T Cells in the Absence of the Thymus. J. Immunol. 175: 4363-4373 [Abstract] [Full Text]
Mandal, M., Borowski, C., Palomero, T., Ferrando, A. A., Oberdoerffer, P., Meng, F., Ruiz-Vela, A., Ciofani, M., Zuniga-Pflucker, J.-C., Screpanti, I., Look, A. T., Korsmeyer, S. J., Rajewsky, K., von Boehmer, H., Aifantis, I. (2005). The BCL2A1 gene as a pre-T cell receptor-induced regulator of thymocyte survival. JEM 201: 603-614 [Abstract] [Full Text]
Weng, A. P., Ferrando, A. A., Lee, W., Morris, J. P. IV, Silverman, L. B., Sanchez-Irizarry, C., Blacklow, S. C., Look, A. T., Aster, J. C. (2004). Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia. Science 306: 269-271 [Abstract] [Full Text]
Ciofani, M., Schmitt, T. M., Ciofani, A., Michie, A. M., Cuburu, N., Aublin, A., Maryanski, J. L., Zuniga-Pflucker, J. C. (2004). Obligatory Role for Cooperative Signaling by Pre-TCR and Notch during Thymocyte Differentiation. J. Immunol. 172: 5230-5239 [Abstract] [Full Text]
Chao, N. J., Emerson, S. G., Weinberg, K. I. (2004). Stem Cell Transplantation (Cord Blood Transplants). ASH Education Book 2004: 354-371 [Abstract] [Full Text]
Garcia-Peydro, M., de Yebenes, V. G., Toribio, M. L. (2003). Sustained Notch1 signaling instructs the earliest human intrathymic precursors to adopt a {gamma}{delta} T-cell fate in fetal thymus organ culture. Blood 102: 2444-2451 [Abstract] [Full Text]
Adler, S. H., Chiffoleau, E., Xu, L., Dalton, N. M., Burg, J. M., Wells, A. D., Wolfe, M. S., Turka, L. A., Pear, W. S. (2003). Notch Signaling Augments T Cell Responsiveness by Enhancing CD25 Expression. J. Immunol. 171: 2896-2903 [Abstract] [Full Text]
Huang, E. Y., Gallegos, A. M., Richards, S. M., Lehar, S. M., Bevan, M. J. (2003). Surface Expression of Notch1 on Thymocytes: Correlation with the Double-Negative to Double-Positive Transition. J. Immunol. 171: 2296-2304 [Abstract] [Full Text]
Schroeder, T., Kohlhof, H., Rieber, N., Just, U. (2003). Notch Signaling Induces Multilineage Myeloid Differentiation and Up-Regulates PU.1 Expression. J. Immunol. 170: 5538-5548 [Abstract] [Full Text]
Klein, F., Feldhahn, N., Lee, S., Wang, H., Ciuffi, F., von Elstermann, M., Toribio, M. L., Sauer, H., Wartenberg, M., Barath, V. S., Kronke, M., Wernet, P., Rowley, J. D., Muschen, M. (2003). T lymphoid differentiation in human bone marrow. Proc. Natl. Acad. Sci. USA 100: 6747-6752 [Abstract] [Full Text]
Asnafi, V., Beldjord, K., Boulanger, E., Comba, B., Le Tutour, P., Estienne, M.-H., Davi, F., Landman-Parker, J., Quartier, P., Buzyn, A., Delabesse, E., Valensi, F., Macintyre, E. (2003). Analysis of TCR, pTalpha , and RAG-1 in T-acute lymphoblastic leukemias improves understanding of early human T-lymphoid lineage commitment. Blood 101: 2693-2703 [Abstract] [Full Text]
Kunisato, A., Chiba, S., Nakagami-Yamaguchi, E., Kumano, K., Saito, T., Masuda, S., Yamaguchi, T., Osawa, M., Kageyama, R., Nakauchi, H., Nishikawa, M., Hirai, H. (2003). HES-1 preserves purified hematopoietic stem cells ex vivo and accumulates side population cells in vivo. Blood 101: 1777-1783 [Abstract] [Full Text]
De Smedt, M., Reynvoet, K., Kerre, T., Taghon, T., Verhasselt, B., Vandekerckhove, B., Leclercq, G., Plum, J. (2002). Active Form of Notch Imposes T Cell Fate in Human Progenitor Cells. J. Immunol. 169: 3021-3029 [Abstract] [Full Text]
Engel, I., Murre, C. (2002). Disruption of pre-TCR expression accelerates lymphomagenesis in E2A-deficient mice. Proc. Natl. Acad. Sci. USA 99: 11322-11327 [Abstract] [Full Text]
Panigada, M., Porcellini, S., Barbier, E., Hoeflinger, S., Cazenave, P.-A., Gu, H., Band, H., von Boehmer, H., Grassi, F. (2002). Constitutive Endocytosis and Degradation of the Pre-T Cell Receptor. JEM 195: 1585-1597 [Abstract] [Full Text]
Stier, S., Cheng, T., Dombkowski, D., Carlesso, N., Scadden, D. T. (2002). Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favors lymphoid over myeloid lineage outcome. Blood 99: 2369-2378 [Abstract] [Full Text]
Bellavia, D., Campese, A. F., Checquolo, S., Balestri, A., Biondi, A., Cazzaniga, G., Lendahl, U., Fehling, H. J., Hayday, A. C., Frati, L., von Boehmer, H., Gulino, A., Screpanti, I. (2002). Combined expression of pTalpha and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis. Proc. Natl. Acad. Sci. USA 99: 3788-3793 [Abstract] [Full Text]
Jaleco, A. C., Neves, H., Hooijberg, E., Gameiro, P., Clode, N., Haury, M., Henrique, D., Parreira, L. (2001). Differential Effects of Notch Ligands Delta-1 and Jagged-1 in Human Lymphoid Differentiation. JEM 194: 991-1002 [Abstract] [Full Text]
von Boehmer, H. (2001). Coming to Grips with Notch. JEM 194: F43-F46 [Full Text]