SEARCH:   Advanced

Blood, 15 November 2007, Vol. 110, No. 10, pp. 3706-3714. Prepublished online as a Blood First Edition Paper on August 1, 2007; DOI 10.1182/blood-2007-02-073486. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2007-02-073486v1 110/10/3706    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 Wouters, B. J. Articles by Delwel, R. Search for Related Content PubMed PubMed Citation Articles by Wouters, B. J. Articles by Delwel, R. Related Collections Neoplasia Gene Expression Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Distinct gene expression profiles of acute myeloid/T-lymphoid leukemia with silenced CEBPA and mutations in NOTCH1 Bas J. Wouters1, Meritxell Alberich Jordà2, Karen Keeshan3, Irene Louwers1, Claudia A. J. Erpelinck-Verschueren1, Dennis Tielemans4, Anton W. Langerak4, Yiping He3, Yumi Yashiro-Ohtani3, Pu Zhang2, Christopher J. Hetherington2, Roel G. W. Verhaak1, Peter J. M. Valk1, Bob Löwenberg1, Daniel G. Tenen2, Warren S. Pear3, and Ruud Delwel1 1 Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands; 2 Harvard Institutes of Medicine, Boston, MA; 3 Abramson Family Cancer Research Institute and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia; and 4 Department of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands Gene expression profiling of acute myeloid leukemia (AML) allows the discovery of previously unrecognized molecular entities. Here, we identified a specific subgroup of AML, defined by an expression profile resembling that of AMLs with mutations in the myeloid transcription factor CCAAT/enhancer-binding protein alpha (C/EBP), while lacking such mutations. We found that in these leukemias, the CEBPA gene was silenced, which was associated with frequent promoter hypermethylation. The leukemias phenotypically showed aberrant expression of T-cell genes, of which CD7 was most consistent. We identified 2 mechanisms that may contribute to this phenotype. First, absence of Cebpa led to up-regulation of specific T-cell transcripts (ie, Cd7 and Lck) in hematopoietic stem cells isolated from conditional Cebpa knockout mice. Second, the enhanced expression of TRIB2, which we identify here as a direct target of the T-cell commitment factor NOTCH1, suggested aberrantly activated Notch signaling. Putatively activating NOTCH1 mutations were found in several specimens of the newly identified subgroup, while a large set of control AMLs was mutation negative. A gene expression prediction signature allowed the detection of similar cases of leukemia in independent series of AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: C/EBPA methylation is common in T-ALL but not in M0 AML Louis Terriou, Raouf Ben Abdelali, Christophe Roumier, Ludovic Lhermitte, John de Vos, Pascale Cornillet, Olivier Nibourel, Kheira Beldjord, Hervé Dombret, Guy Leverger, Vahid Asnafi, Claude Preudhomme, and Elizabeth Macintyre Blood 2009 113: 1864-1866. [Full Text] [PDF] This article has been cited by other articles: T. Pabst and B. U. Mueller Complexity of CEBPA Dysregulation in Human Acute Myeloid Leukemia Clin. Cancer Res., September 1, 2009; 15(17): 5303 - 5307. [Abstract] [Full Text] [PDF] C. R. Geest, M. Buitenhuis, E. Vellenga, and P. J. Coffer Ectopic expression of C/EBP{alpha} and ID1 is sufficient to restore defective neutrophil development in low-risk myelodysplasia Haematologica, August 1, 2009; 94(8): 1075 - 1084. [Abstract] [Full Text] [PDF] I. H. I. M. Hollink, M. M. van den Heuvel-Eibrink, and C. M. Zwaan CEBPA resembles Roman god Janus Blood, June 25, 2009; 113(26): 6501 - 6502. [Full Text] [PDF] B. J. Wouters, B. Lowenberg, C. A. J. Erpelinck-Verschueren, W. L. J. van Putten, P. J. M. Valk, and R. Delwel Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome Blood, March 26, 2009; 113(13): 3088 - 3091. [Abstract] [Full Text] [PDF] M. E. Figueroa, B. J. Wouters, L. Skrabanek, J. Glass, Y. Li, C. A. J. Erpelinck-Verschueren, A. W. Langerak, B. Lowenberg, M. Fazzari, J. M. Greally, et al. Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features Blood, March 19, 2009; 113(12): 2795 - 2804. [Abstract] [Full Text] [PDF] B. Wouters and R. Delwel Response: CEBPA promoter hypermethylation in a subset of myeloid/T-lymphoid leukemias with a distinct gene expression profile Blood, February 19, 2009; 113(8): 1866 - 1866. [Full Text] [PDF] L. Terriou, R. Ben Abdelali, C. Roumier, L. Lhermitte, J. de Vos, P. Cornillet, O. Nibourel, K. Beldjord, H. Dombret, G. Leverger, et al. C/EBPA methylation is common in T-ALL but not in M0 AML Blood, February 19, 2009; 113(8): 1864 - 1866. [Full Text] [PDF] S. Koschmieder, B. Halmos, E. Levantini, and D. G. Tenen Dysregulation of the C/EBP{alpha} Differentiation Pathway in Human Cancer J. Clin. Oncol., February 1, 2009; 27(4): 619 - 628. [Abstract] [Full Text] [PDF] S. Chiaretti and R. Foa T-cell acute lymphoblastic leukemia Haematologica, February 1, 2009; 94(2): 160 - 162. [Full Text] [PDF] B. J. Wouters, B. Lowenberg, and R. Delwel A decade of genome-wide gene expression profiling in acute myeloid leukemia: flashback and prospects Blood, January 8, 2009; 113(2): 291 - 298. [Abstract] [Full Text] [PDF] R. G.W. Verhaak, B. J. Wouters, C. A.J. Erpelinck, S. Abbas, H. B. Beverloo, S. Lugthart, B. Lowenberg, R. Delwel, and P. J.M. Valk Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling Haematologica, January 1, 2009; 94(1): 131 - 134. [Abstract] [Full Text] [PDF] K. Dohner and H. Dohner Molecular characterization of acute myeloid leukemia Haematologica, July 1, 2008; 93(7): 976 - 982. [Full Text] [PDF] B. Hackanson, K. L. Bennett, R. M. Brena, J. Jiang, R. Claus, S.-S. Chen, N. Blagitko-Dorfs, K. Maharry, S. P. Whitman, T. D. Schmittgen, et al. Epigenetic Modification of CCAAT/Enhancer Binding Protein {alpha} Expression in Acute Myeloid Leukemia Cancer Res., May 1, 2008; 68(9): 3142 - 3151. [Abstract] [Full Text] [PDF] S. Strehl, K. Nebral, M. Konig, J. Harbott, H. Strobl, R. Ratei, S. Struski, B. Bielorai, M. Lessard, M. Zimmermann, et al. ETV6-NCOA2: A Novel Fusion Gene in Acute Leukemia Associated with Coexpression of T-Lymphoid and Myeloid Markers and Frequent NOTCH1 Mutations Clin. Cancer Res., February 15, 2008; 14(4): 977 - 983. [Abstract] [Full Text] [PDF] B. Lowenberg Acute Myeloid Leukemia: The Challenge of Capturing Disease Variety Hematology, January 1, 2008; 2008(1): 1 - 11. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020