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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3520-3529. Prepublished online as a Blood First Edition Paper on July 27, 2006; DOI 10.1182/blood-2006-04-019927. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-019927v1 108/10/3520    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 Van Vlierberghe, P. Articles by Pieters, R. Search for Related Content PubMed PubMed Citation Articles by Van Vlierberghe, P. Articles by Pieters, R. Related Collections Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA The cryptic chromosomal deletion del(11)(p12p13) as a new activation mechanism of LMO2 in pediatric T-cell acute lymphoblastic leukemia Pieter Van Vlierberghe, Martine van Grotel, H. Berna Beverloo, Charles Lee, Tryggvi Helgason, Jessica Buijs-Gladdines, Monique Passier, Elisabeth R. van Wering, Anjo J. P. Veerman, Willem A. Kamps, Jules P. P. Meijerink, and Rob Pieters From the Department of Pediatric Oncology/Hematology, Erasmus Medical Center (MC)/Sophia Children's Hospital, Rotterdam, The Netherlands; the Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands; the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; the Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands; the Department of Pediatric Oncology/Hematology, Vrije Universiteit MC, Amsterdam, The Netherlands; and the Department of Pediatric Oncology, Beatrix Children's Hospital, University MC, Groningen, The Netherlands. To identify new cytogenetic abnormalities associated with leukemogenesis or disease outcome, T-cell acute lymphoblastic leukemia (T-ALL) patient samples were analyzed by means of the array-comparative genome hybridization technique (array-CGH). Here, we report the identification of a new recurrent and cryptic deletion on chromosome 11 (del(11)(p12p13)) in about 4% (6/138) of pediatric T-ALL patients. Detailed molecular-cytogenetic analysis revealed that this deletion activates the LMO2 oncogene in 4 of 6 del(11)(p12p13)-positive T-ALL patients, in the same manner as in patients with an LMO2 translocation (9/138). The LMO2 activation mechanism of this deletion is loss of a negative regulatory region upstream of LMO2, causing activation of the proximal LMO2 promoter. LMO2 rearrangements, including this del(11)(p12p13) and t(11;14) (p13;q11) or t(7;11)(q35;p13), were found in the absence of other recurrent cytogenetic abnormalities involving HOX11L2, HOX11, CALM-AF10, TAL1, MLL, or MYC. LMO2 abnormalities represent about 9% (13/138) of pediatric T-ALL cases and are more frequent in pediatric T-ALL than appreciated until now. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. H. I. M. Hollink, M. M. van den Heuvel-Eibrink, M. Zimmermann, B. V. Balgobind, S. T. C. J. M. Arentsen-Peters, M. Alders, A. Willasch, G. J. L. Kaspers, J. Trka, A. Baruchel, et al. Clinical relevance of Wilms tumor 1 gene mutations in childhood acute myeloid leukemia Blood, June 4, 2009; 113(23): 5951 - 5960. [Abstract] [Full Text] [PDF] A. Appert, C.-H. Nam, N. Lobato, E. Priego, R. N. Miguel, T. Blundell, L. Drynan, H. Sewell, T. Tanaka, and T. Rabbitts Targeting LMO2 with a Peptide Aptamer Establishes a Necessary Function in Overt T-Cell Neoplasia Cancer Res., June 1, 2009; 69(11): 4784 - 4790. [Abstract] [Full Text] [PDF] P. Van Vlierberghe, M. van Grotel, J. Tchinda, C. Lee, H. B. Beverloo, P. J. van der Spek, A. Stubbs, J. Cools, K. Nagata, M. Fornerod, et al. The recurrent SET-NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemia Blood, May 1, 2008; 111(9): 4668 - 4680. [Abstract] [Full Text] [PDF] B. V. Balgobind, P. Van Vlierberghe, A. M. W. van den Ouweland, H. B. Beverloo, J. N. R. Terlouw-Kromosoeto, E. R. van Wering, D. Reinhardt, M. Horstmann, G. J. L. Kaspers, R. Pieters, et al. Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis Blood, April 15, 2008; 111(8): 4322 - 4328. [Abstract] [Full Text] [PDF] E. Clappier, W. Cuccuini, A. Kalota, A. Crinquette, J.-M. Cayuela, W. A. Dik, A. W. Langerak, B. Montpellier, B. Nadel, P. Walrafen, et al. The C-MYB locus is involved in chromosomal translocation and genomic duplications in human T-cell acute leukemia (T-ALL), the translocation defining a new T-ALL subtype in very young children Blood, August 15, 2007; 110(4): 1251 - 1261. [Abstract] [Full Text] [PDF]

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