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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.
NEOPLASIA HOX11L2/TLX3 is transcriptionally activated through T-cell regulatory elements downstream of BCL11B as a result of the t(5;14)(q35;q32)From the Institut National de la Santé et de la Recherche Médicale (INSERM), E0210, Paris, France; University René Descartes, Paris, France; INSERM, U768, Paris, France; INSERM, U548, Grenoble, France; CEA-DRDC-laboratoire "Immunochimie," Grenoble, France; Assistance PubliqueHôpitaux de Paris (AH-HP), Laboratoire de Cytogénétique, Hop Necker-Enfants Malades, Paris, France; AP-HP, Service d'Hematologie Biologique, Hop Trousseau, Paris, France; Laboratoire d'Hématologie, Hop de Hautepierre, Strasbourg, France; Laboratoire de Cytogénétique, Institut Paoli-Calmettes, Marseille, France; Université de la Méditerranée, Marseille, France; and Laboratoire de cytogénétique, CHU de Dijon, Dijon, France.
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 8 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, 2 of the 6 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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