Abstract
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.
Publication types
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Clinical Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Differentiation / genetics
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Chromosomes, Human, Pair 14 / genetics*
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Chromosomes, Human, Pair 5 / genetics*
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics*
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Homeodomain Proteins / biosynthesis
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Homeodomain Proteins / genetics*
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Humans
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Jurkat Cells
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Leukemia-Lymphoma, Adult T-Cell / genetics*
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Leukemia-Lymphoma, Adult T-Cell / metabolism
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Leukemia-Lymphoma, Adult T-Cell / pathology
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Oncogene Proteins / biosynthesis
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Oncogene Proteins / genetics*
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Oncogene Proteins, Fusion / biosynthesis
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Oncogene Proteins, Fusion / genetics*
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Promoter Regions, Genetic / genetics
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Repressor Proteins / biosynthesis
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Repressor Proteins / genetics*
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology
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Transcription, Genetic
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Translocation, Genetic*
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Tumor Suppressor Proteins / biosynthesis
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Tumor Suppressor Proteins / genetics*
Substances
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BCL11B protein, human
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DNA-Binding Proteins
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Homeodomain Proteins
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Oncogene Proteins
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Oncogene Proteins, Fusion
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Repressor Proteins
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TLX3 protein, human
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Tumor Suppressor Proteins