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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.
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Submitted April 2, 2007
Accepted June 19, 2007
Prognostic and oncogenic relevance of TLX1/HOX11 expression level in T-ALLs
Julie Bergeron, Emmanuelle Clappier, Isabelle Radford, Agnes Buzyn, Corinne Millien, Gwendoline Soler, Paola Ballerini, Xavier Thomas, Jean Soulier, Herve Dombret, Elizabeth A. Macintyre, and Vahid Asnafi*
Universite Paris V Rene Descartes, INSERM EMI0210, AP-HP Hopital Necker-Enfants-Malades, Paris, France
INSERM U728 IUH and Hematology Laboratory, AP-HP Hopital St-Louis, Paris, France
Hematology Department, AP-HP Hopital Necker-Enfants-Malades, Paris, France
Service d'hematologie biologique, Hopital Armand Trousseau, Paris, France
Department of Hematology, Hopital Edouard Herriot, Lyon, France
Hematology Department, Hopital St-Louis, Paris, France
* Corresponding author; email: vahid.asnafi{at}nck.aphp.fr.
TLX1 is a homeodomain transcription factor generally associated with a favourable outcome in 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 RQ-PCR ratio of TLX1>1.00E+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 harbour molecular TLX1 locus abnormalities in the vast 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 (p=0,035) and a marked trend for longer overall survival (p=0,059) 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 >1 and/or demonstrating TLX1 rearrangement. Therapeutic modification should be considered for those patients.
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