SEARCH:   Advanced

Blood, 15 February 2008, Vol. 111, No. 4, pp. 2321-2328. Prepublished online as a Blood First Edition Paper on December 11, 2007; DOI 10.1182/blood-2007-06-095570. This Article Full Text (PDF) All Versions of this Article: blood-2007-06-095570v1 111/4/2321    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 Le Toriellec, E. Articles by Stern, M.-H. Search for Related Content PubMed PubMed Citation Articles by Le Toriellec, E. Articles by Stern, M.-H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 19, 2007 Accepted November 24, 2007 Haplo-insufficiency of CDKN1B contributes to leukemogenesis in T-cell prolymphocytic leukemia Emilie Le Toriellec, Gilles Despouy, Gaelle Pierron, Nogaye Gaye, Marjorie Joiner, Dorine Bellanger, Anne Vincent-Salomon, and Marc-Henri Stern* Institut Curie, Centre de Recherche, Paris, France INSERM U830, Paris, France Department of Tumor Biology, Institut Curie, Paris, France * Corresponding author; email: marc-henri.stern{at}curie.fr. T-cell prolymphocytic leukemia (T-PLL) is consistently associated with inactivation of the ATM gene and chromosomal rearrangements leading to an over-expression of MTCP1/TCL1 oncoproteins. These alterations are present at the earliest stage of malignant transformation, suggesting that additional events are required for overt malignancy. In this study, we pursued the investigation of the 12p13 deletion, previously shown to occur in approximately half of T-PLLs. We refined the minimal region of deletion by single nucleotide and microsatellite polymorphism allelotyping. We defined a 216kb region containing the CDKN1B gene that encodes the cyclin-dependent kinase inhibitory protein p27KIP1. Sequencing this gene in 47 T-PLL patient samples revealed a nonsense mutation in one case without 12p13 deletion. The absence of bi-allelic inactivation of CDKN1B for most patients suggested a haplo-insufficiency mechanism for tumor suppression, which was investigated in an animal model of the disease. In a Cdkn1b+/- background, MTCP1 transgenics had consistent and multiple emergences of pre-leukemic clones not observed in control cohorts. The second Cdkn1b allele was maintained and expressed in these pre-leukemic clones. Altogether, these data strongly implicate CDKN1B haplo-insufficiency in the pathogenesis of T-PLL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Nowak, E. Le Toriellec, M.-H. Stern, N. Kawamata, T. Akagi, M. J. Dyer, W.-K. Hofmann, S. Ogawa, and H. P. Koeffler Molecular allelokaryotyping of T-cell prolymphocytic leukemia cells with high density single nucleotide polymorphism arrays identifies novel common genomic lesions and acquired uniparental disomy Haematologica, April 1, 2009; 94(4): 518 - 527. [Abstract] [Full Text] [PDF]

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