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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1251-1261. Prepublished online as a Blood First Edition Paper on April 23, 2007; DOI 10.1182/blood-2006-12-064683. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2006-12-064683v1 110/4/1251    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 Clappier, E. Articles by Soulier, J. Search for Related Content PubMed PubMed Citation Articles by Clappier, E. Articles by Soulier, J. Related Collections Neoplasia Oncogenes and Tumor Suppressors Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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 Emmanuelle Clappier1,3, Wendy Cuccuini1,2, Anna Kalota4, Antoine Crinquette1, Jean-Michel Cayuela1,2, Willem A. Dik5, Anton W. Langerak5, Bertrand Montpellier6, Bertrand Nadel6, Pierre Walrafen7, Olivier Delattre8, Alain Aurias8, Thierry Leblanc9, Hervé Dombret10, Alan M. Gewirtz4, André Baruchel10, Franois Sigaux1,2, and Jean Soulier1,2 1 Genome Rearrangements and Cancer Group, Institut National de la Santé et de la Recherche Médicale (INSERM) U728 and Institut Universitaire d'Hématologie, Paris 7 University, Hôpital Saint-Louis, Paris, France; 2 Hematology Laboratory, Assistance Publique Hôpitaux de Paris (APHP), Hôpital Saint-Louis, Paris, France; 3 Laboratoire de Biochimie Génétique, APHP, Hôpital Robert Debré, Paris, France; 4 Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia; 5 Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; 6 Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille, France; 7 Genomic Vision, Pasteur Biotop, Paris, France; 8 INSERM U509, Institut Curie-Section Recherche, Paris, France; 9 Pediatric Hematology Department, APHP, Hôpital Saint-Louis, Paris, France; 10 Adult Hematology Department, APHP, Hôpital Saint-Louis, Paris, France The C-Myb transcription factor is essential for hematopoiesis, including in the T-cell lineage. The C-Myb locus is a common site of retroviral insertional mutagenesis, however no recurrent genomic involvement has been reported in human malignancies. Here, we identified 2 types of genomic alterations involving the C-MYB locus at 6q23 in human T-cell acute leukemia (T-ALL). First, we found a reciprocal translocation, t(6;7)(q23;q34), that juxtaposed the TCRB and C-MYB loci (n = 6 cases). Second, a genome-wide copy-number analysis by array-based comparative genomic hybridization (array-CGH) identified short somatic duplications that include C-MYB (MYBdup, n = 13 cases of 84 T-ALL, 15%). Expression analysis, including allele-specific approaches, showed stronger C-MYB expression in the MYB-rearranged cases compared with other T-ALLs, and a dramatically skewed C-MYB allele expression in the TCRB-MYB cases, which suggests that a translocation-driven deregulated expression may overcome a cellular attempt to down-regulate C-MYB. Strikingly, profiling of the T-ALLs by clinical, genomic, and large-scale gene expression analyses shows that the TCRB-MYB translocation defines a new T-ALL subtype associated with a very young age for T-cell leukemia (median, 2.2 years) and with a proliferation/mitosis expression signature. By contrast, the MYBdup alteration was associated with the previously defined T-ALL subtypes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. R. Lidonnici, F. Corradini, T. Waldron, T. P. Bender, and B. Calabretta Requirement of c-Myb for p210BCR/ABL-dependent transformation of hematopoietic progenitors and leukemogenesis Blood, May 1, 2008; 111(9): 4771 - 4779. [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] J. P. O'Rourke and S. A. Ness Alternative RNA Splicing Produces Multiple Forms of c-Myb with Unique Transcriptional Activities Mol. Cell. Biol., March 15, 2008; 28(6): 2091 - 2101. [Abstract] [Full Text] [PDF] J. O'Neil, J. Tchinda, A. Gutierrez, L. Moreau, R. S. Maser, K.-K. Wong, W. Li, K. McKenna, X. S. Liu, B. Feng, et al. Alu elements mediate MYB gene tandem duplication in human T-ALL J. Exp. Med., December 24, 2007; 204(13): 3059 - 3066. [Abstract] [Full Text] [PDF]

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