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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4198-4201.
Prepublished online as a Blood First Edition Paper on August 22, 2006; DOI 10.1182/blood-2006-07-032953.


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Submitted July 5, 2006
Accepted August 1, 2006

HOX11L2/TLX3 is transcriptionally activated through T-cell regulatory elements downstream of BCL11B as a result of the t(5;14)(q35;q32)

Xin-Ying Su, Veronique Della-Valle, Isabelle Andre-Schmutz, Claudie Lemercier, Isabelle Radford-Weiss, Paola Ballerini, Michel Lessard, Marina Lafage-Pochitaloff, Francine Mugneret, Roland Berger, Serge P Romana, Olivier Bernard, and Virginie Penard-Lacronique*

INSERM0210; Hopital Necker, Paris
INSERM E0210, Hopital Necker, Paris France
INSERM U768, Hopital Necker-Enfants Malades, Paris, France
INSERM U548, CEA-Grenoble/DRDC/ICH, Grenoble France
INSERM E210 and Laboratoire de cytogenetique, Hopital Necker, Paris France
Service d'hematologie, Hopital Trousseau, Paris, France
Laboratoire d'Hematologie, Hopital de hautepierre, Strasbourg, France
Laboratoire de cytogenetique,UMR599, Marseilles, France
Laboratoire de cytogenetique, CHU de Dijon, France
INSERM, E0210 ; Hopital Necker, Paris, France
INSERM
INSERM E0210; Hopital Necker, Paris

* Corresponding author; email: penard{at}necker.fr.

The t(5;14)(q35;q32) chromosomal translocation is specifically observed in up to 20% of childhood T-cell acute lymphoblastic leukemia (T-ALL). It affects the BCL11B/CTIP2 locus on chromosome 14 and the RANBP17-TLX3/HOX11L2 region on chromosome 5. It leads to ectopic activation of TLX3/HOX11L2. To investigate the reasons of the association between t(5;14) and T-ALL, we isolated the translocation breakpoints in eight t(5;14) patients. Sequence analyses did not involve recombinase activity in the genesis of the translocation. We used DNAse1 hypersensitive experiments to locate transcriptional regulatory elements downstream of BCL11B. By transient transfection experiments, two of the six regions demonstrated cis-activation properties in T-cells and were also effective on the TLX3 promoter. Our data indicate that the basis of the specific association between t(5;14) and T-ALL lies on the juxtaposition of TLX3 to long-range cis-activating regions active during T-cell differentiation.


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