SEARCH:   Advanced

Blood, 15 April 2007, Vol. 109, No. 8, pp. 3451-3461. Prepublished online as a Blood First Edition Paper on December 14, 2006; DOI 10.1182/blood-2006-08-041012. This Article Full Text (PDF) Supplemental Table All Versions of this Article: blood-2006-08-041012v1 109/8/3451    most recent Alert me when this article is cited Alert me if a correction is posted 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 Akasaka, T. Articles by Dyer, M. J. Search for Related Content PubMed PubMed Citation Articles by Akasaka, T. Articles by Dyer, M. J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 10, 2006 Accepted December 2, 2006 Five members of the CEBP transcription factor family are targeted by recurrent IGH-translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) Takashi Akasaka, Theodore Balasas, Lisa J Russell, Kei-ji Sugimoto, Aneela Majid, Renata Walewska, E Loraine Karran, David G Brown, Kelvin Cain, Lana Harder, Stefan Gesk, Jose Ignacio Martin-Subero, Mark G Atherton, Monika Bruggemann, Maria Jose Calasanz, Teresa Davies, Oskar A Haas, Anne Hagemeijer, Helena Kempski, Michel Lessard, Debra M Lillington, Sarah Moore, Florence Nguyen-Khac, Isabelle Radford-Weiss, Claudia Schoch, Stephanie Struski, Polly Talley, Melanie J Welham, Helen Worley, Jon C Strefford, Christine J Harrison, Reiner Siebert, and Martin JS Dyer* MRC Toxicology Unit, University of Leicester, Leicester, United Kingdom Leukaemia Research Cytogenetics Group, Cancer Sciences Division, University of Southampton, Southampton, United Kingdom Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany Merseyside & Cheshire Genetics Laboratory, Liverpool Women's Hospital, Liverpool, United Kingdom Second Medical Department, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany Departamento de Genetica, Universidad de Navarra, Pamplona, Spain South West Regional Cytogenetics Centre, Southmead Hospital, Bristol, United Kingdom Children's Cancer Research Institute, Vienna, Austria Center for Human Genetics, Leuven, Belgium Paediatric Malignancy Cytogenetics Laboratory, Great Ormond Street Hospital for Sick Children, London, United Kingdom Laboratoire d'Hematologie, Hopital de Hautepierre, Strasbourg, France Cancer Research UK Medical Oncology Unit, St Bartholomew's Hospital Medical School, Queen Mary University of London, London, United Kingdom SA Cancer Cytogenetics Unit, Institute of Medical and Veterinary Science, Adelaide, Australia Unite de Cytogenetique Hematologique, EO210 INSERM, Groupe Hopitalier Pitie-Salpetriere, Paris, France Unite de Cytogenetique Hematologique, Service d'Histo-Embryologie et de Cytogenetique, Hopital Necker-Enfants Malades, Paris, France MLL Munchner Leukamielabor GmbH, Munich, Germany Sheffield Regional Cytogenetics Service, Sheffield Children's Hospital, Sheffield, United Kingdom Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom * Corresponding author; email: mjsd1{at}le.ac.uk. CCAAT-enhancer-binding-protein (CEBP) transcription factors play pivotal roles in proliferation and differentiation, including suppression of myeloid leukemogenesis. Mutations of CEBPA are found in a subset of acute myeloid leukaemia (AML) and in some cases of familial AML. Here, using cytogenetics, fluorescence in situ hybridization (FISH) and molecular cloning, we show that five CEBP gene family members are targeted by recurrent IGH chromosomal translocations in BCP-ALL. Ten cases with t(8;14)(q11;q32) involved CEBPD on chromosome 8, nine cases with t(14;19)(q32;q13) involved CEBPA, whilst a further case involved CEBPG, located 71kb telomeric of CEBPA on chromosome band,19q13; four cases with inv(14)(q11q32)/t(14;14)(q11;q32) involved CEBPE and three with t(14;20)(q32;q13), CEBPB. In 16 cases the translocation breakpoints were cloned using long-distance inverse (LDI-) PCR. With the exception of CEBPD breakpoints, which were scattered within a 43kb region centromeric of CEBPD, translocation breakpoints were clustered immediately 5' or 3' of the involved CEBP gene. Except in one case with t(14;14)(q11;q32), the involved CEBP genes retained germline sequences. Quantitative RT-PCR showed over-expression of the translocated CEBP gene. Our findings implicate the CEBP gene family as novel oncogenes in BCP-ALL, and suggest opposing functions of CEBP dysregulation in myeloid and lymphoid leukemogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. J. Russell, M. Capasso, I. Vater, T. Akasaka, O. A. Bernard, M. J. Calasanz, T. Chandrasekaran, E. Chapiro, S. Gesk, M. Griffiths, et al. Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia Blood, September 24, 2009; 114(13): 2688 - 2698. [Abstract] [Full Text] [PDF] 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] I. Nagel, T. Akasaka, W. Klapper, S. Gesk, S. Bottcher, M. Ritgen, L. Harder, M. Kneba, M. J.S. Dyer, and R. Siebert Identification of the gene encoding cyclin E1 (CCNE1) as a novel IGH translocation partner in t(14;19)(q32;q12) in diffuse large B-cell lymphoma Haematologica, July 1, 2009; 94(7): 1020 - 1023. [Abstract] [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] C. Forni, M. Minuzzo, E. Virdis, E. Tamborini, M. Simone, M. Tavecchio, E. Erba, F. Grosso, A. Gronchi, P. Aman, et al. Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors Mol. Cancer Ther., February 1, 2009; 8(2): 449 - 457. [Abstract] [Full Text] [PDF] S. Sulong, A. V. Moorman, J. A. E. Irving, J. C. Strefford, Z. J. Konn, M. C. Case, L. Minto, K. E. Barber, H. Parker, S. L. Wright, et al. A comprehensive analysis of the CDKN2A gene in childhood acute lymphoblastic leukemia reveals genomic deletion, copy number neutral loss of heterozygosity, and association with specific cytogenetic subgroups Blood, January 1, 2009; 113(1): 100 - 107. [Abstract] [Full Text] [PDF] E. Forestier, S. Izraeli, B. Beverloo, O. Haas, A. Pession, K. Michalova, B. Stark, C. J. Harrison, A. Teigler-Schlegel, and B. Johansson Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome: an iBFM-SG study Blood, February 1, 2008; 111(3): 1575 - 1583. [Abstract] [Full Text] [PDF] A. Majid, O. Tsoulakis, R. Walewska, S. Gesk, R. Siebert, D. B. J. Kennedy, and M. J. S. Dyer BCL2 expression in chronic lymphocytic leukemia: lack of association with the BCL2 938A>C promoter single nucleotide polymorphism Blood, January 15, 2008; 111(2): 874 - 877. [Abstract] [Full Text] [PDF] L. J. Russell, T. Akasaka, A. Majid, K.-j. Sugimoto, E. Loraine Karran, I. Nagel, L. Harder, A. Claviez, S. Gesk, A. V. Moorman, et al. t(6;14)(p22;q32): a new recurrent IGH@ translocation involving ID4 in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) Blood, January 1, 2008; 111(1): 387 - 391. [Abstract] [Full Text] [PDF] B. J. Wouters, M. A. Jorda, K. Keeshan, I. Louwers, C. A. J. Erpelinck-Verschueren, D. Tielemans, A. W. Langerak, Y. He, Y. Yashiro-Ohtani, P. Zhang, et al. Distinct gene expression profiles of acute myeloid/T-lymphoid leukemia with silenced CEBPA and mutations in NOTCH1 Blood, November 15, 2007; 110(10): 3706 - 3714. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020