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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2324-2330. Prepublished online as a Blood First Edition Paper on July 3, 2007; DOI 10.1182/blood-2007-04-079988. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-04-079988v1 110/7/2324    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bergeron, J. Articles by Asnafi, V. Search for Related Content PubMed PubMed Citation Articles by Bergeron, J. Articles by Asnafi, V. Related Collections Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Prognostic and oncogenic relevance of TLX1/HOX11 expression level in T-ALLs Julie Bergeron1, Emmanuelle Clappier2, Isabelle Radford1, Agnès Buzyn3, Corinne Millien1, Gwendoline Soler1, Paola Ballerini4, Xavier Thomas5, Jean Soulier2, Hervé Dombret6, Elizabeth A. Macintyre1, and Vahid Asnafi1 1 The Université Paris V René Descartes, Institut National de la Santé et de la Recherche Médicale (INSERM) EMI0210 and Assistance Publique–Hôpitaux de Paris (AP-HP) Hôpital Necker-Enfants-Malades, Paris; 2 INSERM U728 Unité d'immuno-hématologie (UIH) and Hematology Laboratory AP-HP Hôpital St-Louis, Paris; 3 Hematology Department Hôpital Necker-Enfants-Malades, Paris; 4 Service d'hématologie biologique Hôpital Armand Trousseau, Paris; 5 Department of Hematology Hôpital Edouard Herriot, Lyon; 6 Hematology Department Hôpital St-Louis, Paris, France TLX1 is a homeodomain transcription factor generally associated with a favorable outcome in T-cell acute lymphoblastic leukemia (T-ALL). However, the molecular mechanisms of TLX1 deregulation remain unclear and various transcript levels in the absence of 10q24 abnormalities have been reported. A reproducible and accurate delineation of TLX1+ T-ALL will be necessary for proper therapeutic stratification. We have studied 264 unselected T-ALLs (171 adults and 93 children) and show that T-ALLs expressing high levels of TLX1 (n = 35, 13%), defined as a real-time quantitative polymerase chain reaction (RQ-PCR) level of TLX1 greater than 1.00 ABL, form a homogeneous oncogenic group, based on their uniform stage of maturation arrest and oncogenetic and transcriptional profiles. Furthermore, TLX1-high T-ALLs harbor molecular TLX1 locus abnormalities in the majority (31/33), a proportion largely underestimated by standard karyotypic screening. T-ALLs expressing TLX1 at lower levels (n = 57, 22%) do not share these characteristics. Prognostic analysis within the adult LALA94 and GRAALL03 prospective protocols demonstrate a better event-free survival (P = .035) and a marked trend for longer overall survival (P = .059) for TLX1-high T-ALLs, while the expression of lower levels of TLX1 does not impact on prognosis. We propose that TLX1+ T-ALLs be defined as cases expressing TLX1/ABL ratios greater than 1 and/or demonstrating TLX1 rearrangement. Therapeutic modification should be considered for those patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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