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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 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 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 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. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Haploinsufficiency of CDKN1B contributes to leukemogenesis in T-cell prolymphocytic leukemia Emilie Le Toriellec1,2, Gilles Despouy1,2, Gaëlle Pierron1,2, Nogaye Gaye1,2, Marjorie Joiner1,2, Dorine Bellanger1,2, Anne Vincent-Salomon3, and Marc-Henri Stern1,2 1 Institut Curie, Centre de Recherche, Paris; 2 Inserm U830, Paris; and 3 Institut Curie, Department of Tumor Biology, Paris, France T-cell prolymphocytic leukemia (T-PLL) is consistently associated with inactivation of the ATM gene and chromosomal re-arrangements leading to an overexpression 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 216-kb 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 biallelic inactivation of CDKN1B for most patients suggested a haploinsufficiency 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 preleukemic clones not observed in control cohorts. The second Cdkn1b allele was maintained and expressed in these preleukemic clones. Altogether, these data strongly implicate CDKN1B haploinsufficiency 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]

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