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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 26, 2006 Accepted April 19, 2007 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 Clappier, Wendy Cuccuini, Anna Kalota, Antoine Crinquette, Jean-Michel Cayuela, Willem A Dik, Anton W Langerak, Bertrand Montpellier, Bertrand Nadel, Pierre Walrafen, Olivier Delattre, Alain Aurias, Thierry Leblanc, Herve Dombret, Alan M Gewirtz, Andre Baruchel, Francois Sigaux, and Jean Soulier* Laboratoire de Biochimie Genetique, APHP, Hopital Robert Debre, Paris, France Genome Rearrangements and Cancer Group, INSERM U728 and Institut Universitaire d'Hematologie, Paris 7 University, Hopital Saint-Louis, Paris, France Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, United States Hematology Laboratory, APHP, Hopital Saint-Louis, Paris, France Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, Netherlands Centre d'immunologie de Marseille Luminy (CIML) INSERM-CNRS, Universite de la Mediterranee, Marseille, France Genomic Vision, Institut Pasteur, Paris, France Section Recherche, INSERM U509, Institut Curie, Paris, France Pediatric Hematology Department, APHP, Hopital Saint-Louis, Paris, France Adult Hematology Department, APHP, Hopital Saint-Louis, Paris, France * Corresponding author; email: jean.soulier{at}sls.aphp.fr. The c-Myb transcription factor is essential for primitive and adult 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 two 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-CGH identified short somatic duplications which include C-MYB (MYBdup, n=13 cases out of 84 T-ALL, 15%). Expression analysis, including allele-specific approaches, showed stronger C-MYB expression in the MYB-rearranged cases compared to 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 downregulate 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-old) and with a proliferation/mitosis expression signature. By contrast, the MYBdup alteration was associated to 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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