HOX11L2/TLX3 is transcriptionally activated through T-cell regulatory elements downstream of BCL11B as a result of the t(5;14)(q35;q32).
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.
Su
Xin-Ying
XY
Institut National de la Santé et de la Recherche Médicale (INSERM), E0210, Paris, France.
Della-Valle
Véronique
V
Andre-Schmutz
Isabelle
I
Lemercier
Claudie
C
Radford-Weiss
Isabelle
I
Ballerini
Paola
P
Lessard
Michel
M
Lafage-Pochitaloff
Marina
M
Mugneret
Francine
F
Berger
Roland
R
Romana
Serge P
SP
Bernard
Olivier A
OA
Penard-Lacronique
Virginie
V
D002454:Cell Differentiation / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*
C479740:BCL11B protein, human; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D012097:Repressor Proteins; C489494:TLX3 protein, human; D025521:Tumor Suppressor Proteins